Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases

  • Savage, P. A., Klawon, D. E. J. & Miller, C. H. Regulatory T cell improvement. Annu. Rev. Immunol. 38, 421–453 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nishizuka, Y. & Sakakura, T. Thymus and replica: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166, 753–755 (1969).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, H. et al. Ldl cholesterol suppresses human iTreg differentiation and nTreg operate via mitochondria-related mechanisms. J. Transl. Med. 21, 224 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • van der Veeken, J. et al. Genetic tracing reveals transcription issue Foxp3-dependent and Foxp3-independent performance of peripherally induced Treg cells. Immunity 55, 1173–1184.e1177 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bluestone, J. A., McKenzie, B. S., Beilke, J. & Ramsdell, F. Alternatives for Treg cell remedy for the therapy of human illness. Entrance. Immunol. 14, 1166135 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sakaguchi, S. et al. Regulatory T cells and human illness. Annu. Rev. Immunol. 38, 541–566 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wing, Okay. et al. CTLA-4 management over Foxp3+ regulatory T cell operate. Science 322, 271–275 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tekguc, M. et al. Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells. Proc. Natl. Acad. Sci. USA. 118, e2023739118 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gertel, S., Polachek, A., Elkayam, O. & Furer, V. Lymphocyte activation gene-3 (LAG-3) regulatory T cells: an evolving biomarker for therapy response in autoimmune ailments. Autoimmun. Rev. 21, 103085 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Huang, C. T. et al. Function of LAG-3 in regulatory T cells. Immunity 21, 503–513 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Akkaya, B. et al. Regulatory T cells mediate particular suppression by depleting peptide-MHC class II from dendritic cells. Nat. Immunol. 20, 218–231 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cao, X. et al. Granzyme B and perforin are necessary for regulatory T cell-mediated suppression of tumor clearance. Immunity 27, 635–646 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rubtsov, Y. P. et al. Regulatory T cell-derived interleukin-10 limits irritation at environmental interfaces. Immunity 28, 546–558 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Collison, L. W. et al. IL-35-mediated induction of a potent regulatory T cell inhabitants. Nat. Immunol. 11, 1093–1101 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Timperi, E. & Barnaba, V. CD39 regulation and features in T cells. Int. J. Mol. Sci. 22, 8068 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Borsellino, G. et al. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110, 1225–1232 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chinen, T. et al. An important function for the IL-2 receptor in T(reg) cell operate. Nat. Immunol. 17, 1322–1333 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cusick, M. F., Libbey, J. E. & Fujinami, R. S. Molecular mimicry as a mechanism of autoimmune illness. Clin. Rev. Allergy Immunol. 42, 102–111 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Klawon, D. E. J. et al. Regulatory T cells constrain T cells of shared specificity to implement tolerance throughout an infection. Science 387, eadk3248 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Feuerer, M. et al. Lean, however not overweight, fats is enriched for a singular inhabitants of regulatory T cells that have an effect on metabolic parameters. Nat. Med. 15, 930–939 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Panduro, M., Benoist, C. & Mathis, D. Tissue Tregs. Annu. Rev. Immunol. 34, 609–633 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Burzyn, D. et al. A particular inhabitants of regulatory T cells potentiates muscle restore. Cell 155, 1282–1295 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kuswanto, W. et al. Poor restore of skeletal muscle in growing older mice displays a defect in native, interleukin-33-dependent accumulation of regulatory T cells. Immunity 44, 355–367 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shevach, E. M. & Thornton, A. M. tTregs, pTregs, and iTregs: similarities and variations. Immunol. Rev. 259, 88–102 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sakaguchi, S., Takahashi, T. & Nishizuka, Y. Examine on mobile occasions in postthymectomy autoimmune oophoritis in mice. I. Requirement of Lyt-1 effector cells for oocytes injury after adoptive switch. J. Exp. Med. 156, 1565–1576 (1982).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sakaguchi, S. et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes numerous autoimmune ailments. J. Immunol. 155, 1151–1164 (1995).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim, C. H. FOXP3 and its function within the immune system. Adv. Exp. Med. Biol. 665, 17–29 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bennett, C. L. et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is attributable to mutations of FOXP3. Nat. Genet. 27, 20–21 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hori, S., Nomura, T. & Sakaguchi, S. Management of regulatory T cell improvement by the transcription issue Foxp3. Science 299, 1057–1061 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fontenot, J. D., Gavin, M. A. & Rudensky, A. Y. Foxp3 packages the event and performance of CD4+CD25+ regulatory T cells. Nat. Immunol. 4, 330–336 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Khattri, R., Cox, T., Yasayko, S. A. & Ramsdell, F. An important function for Scurfin in CD4+CD25+T regulatory cells. Nat. Immunol. 4, 337–342 (2003).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Williams, L. M. & Rudensky, A. Y. Upkeep of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat. Immunol. 8, 277–284 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, J. et al. Human FOXP3 and tumour microenvironment. Immunology 168, 248–255 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sumida, T. S., Cheru, N. T. & Hafler, D. A. The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune ailments. Nat. Rev. Immunol. 24, 503–517 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Toomer, Okay. H. et al. Important and non-overlapping IL-2Rα-dependent processes for thymic improvement and peripheral homeostasis of regulatory T cells. Nat. Commun. 10, 1037 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dikiy, S. et al. A distal Foxp3 enhancer permits interleukin-2 dependent thymic Treg cell lineage dedication for strong immune tolerance. Immunity 54, 931–946.e911 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kawakami, R. et al. Distinct Foxp3 enhancer parts coordinate improvement, upkeep, and performance of regulatory T cells. Immunity 54, 947–961.e948 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tang, S. et al. A lncRNA Dleu2-encoded peptide relieves autoimmunity by facilitating Smad3-mediated Treg induction. EMBO Rep. 25, 1208–1232 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schlenner, S. M. et al. Smad3 binding to the foxp3 enhancer is dispensable for the event of regulatory T cells except for the intestine. J. Exp. Med. 209, 1529–1535 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kaminski, A. et al. Resident regulatory T cells replicate the immune historical past of particular person lymph nodes. Sci. Immunol. 8, eadj5789 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liston, A., Dooley, J. & Yshii, L. Mind-resident regulatory T cells and their function in well being and illness. Immunol. Lett. 248, 26–30 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ramanan, D. et al. Regulatory T cells within the face of the intestinal microbiota. Nat. Rev. Immunol. 23, 749–762 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Thornton, A. M. et al. Helios(+) and Helios(-) Treg subpopulations are phenotypically and functionally distinct and categorical dissimilar TCR repertoires. Eur. J. Immunol. 49, 398–412 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Campos-Mora, M. et al. Neuropilin-1 is current on Foxp3+ T regulatory cell-derived small extracellular vesicles and mediates immunity towards pores and skin transplantation. J. Extracell. Vesicles 11, e12237 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yu, F. et al. Dynamic expression of transcription components T-bet and GATA-3 by regulatory T cells maintains immunotolerance. Nat. Immunol. 16, 197–206 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zheng, Y. et al. Regulatory T-cell suppressor program co-opts transcription issue IRF4 to manage T(H)2 responses. Nature 458, 351–356 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zeng, Q. et al. A singular inhabitants: adipose-resident regulatory T cells. Entrance. Immunol. 9, 2075 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bapat, S. P. et al. Depletion of fat-resident Treg cells prevents age-associated insulin resistance. Nature 528, 137–141 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cipolletta, D. et al. PPAR-γ is a serious driver of the buildup and phenotype of adipose tissue Treg cells. Nature 486, 549–553 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dominguez-Villar, M., Baecher-Allan, C. M. & Hafler, D. A. Identification of T helper sort 1-like, Foxp3+ regulatory T cells in human autoimmune illness. Nat. Med. 17, 673–675 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pesenacker, A. M. et al. CD161 defines the subset of FoxP3+ T cells able to producing proinflammatory cytokines. Blood 121, 2647–2658 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Floess, S. et al. Epigenetic management of the foxp3 locus in regulatory T cells. PLoS Biol. 5, e38 (2007).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Povoleri, G. A. M. et al. Human retinoic acid-regulated CD161(+) regulatory T cells assist wound restore in intestinal mucosa. Nat. Immunol. 19, 1403–1414 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tang, X. et al. Phenotype, operate, and scientific significance of CD26+ and CD161+Tregs in splenic marginal zone lymphoma. Clin. Most cancers Res. 28, 4322–4335 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Neuwirth, T. et al. The polyamine-regulating enzyme SSAT1 impairs tissue regulatory T cell operate in power cutaneous irritation. Immunity 58, 632–647.e612 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shan, F. et al. Therapeutic focusing on of regulatory T cells in most cancers. Developments Most cancers 8, 944–961 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Miyao, T. et al. Plasticity of Foxp3(+) T cells displays promiscuous Foxp3 expression in standard T cells however not reprogramming of regulatory T cells. Immunity 36, 262–275 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, J. et al. Transient expression of FOXP3 in human activated nonregulatory CD4+T cells. Eur. J. Immunol. 37, 129–138 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Allan, S. E. et al. Activation-induced FOXP3 in human T effector cells doesn’t suppress proliferation or cytokine manufacturing. Int. Immunol. 19, 345–354 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tran, D. Q., Ramsey, H. & Shevach, E. M. Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is reworking progress factor-beta dependent however doesn’t confer a regulatory phenotype. Blood 110, 2983–2990 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zemmour, D. et al. Single-cell evaluation of FOXP3 deficiencies in people and mice unmasks intrinsic and extrinsic CD4(+) T cell perturbations. Nat. Immunol. 22, 607–619 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Roncarolo, M. G. et al. The biology of T regulatory sort 1 cells and their therapeutic utility in immune-mediated ailments. Immunity 49, 1004–1019 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gagliani, N. et al. Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory sort 1 cells. Nat. Med. 19, 739–746 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Raverdeau, M. et al. Retinoic acid-induced autoantigen-specific sort 1 regulatory T cells suppress autoimmunity. EMBO Rep. 20, e47121 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Umeshappa, C. S. et al. Liver-specific T regulatory type-1 cells program native neutrophils to suppress hepatic autoimmunity by way of CRAMP. Cell Rep. 34, 108919 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sultan, H. et al. Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress most cancers immunotherapy. Nature 632, 182–191 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Malek, T. R. & Castro, I. Interleukin-2 receptor signaling: on the interface between tolerance and immunity. Immunity 33, 153–165 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ju, B. et al. The proportion and phenotypic modifications of CD4(+)CD25(-)Foxp3(+) T cells in sufferers with untreated rheumatoid arthritis. BMC Immunol. 23, 41 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, X. & Oppenheim, J. J. Resolving the identification fantasy: key markers of useful CD4+FoxP3+ regulatory T cells. Int. Immunopharmacol. 11, 1489–1496 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Luo, S. et al. Foxp3(+)CD8(+) regulatory T cells: bona fide Tregs with cytotoxic operate. Developments Immunol. 46, 324–337 (2025).

  • Liu, W. et al. CD127 expression inversely correlates with FoxP3 and suppressive operate of human CD4+T reg cells. J. Exp. Med. 203, 1701–1711 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, M. S. et al. A comparability on viability between CD4+T cells and CD4+CD25+CD127- regulatory T cells by excimer laser within the peripheral blood in vitro. Photodermatol. Photoimmunol. Photomed. 37, 247–249 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Walter, G. J. et al. Phenotypic, useful, and gene expression profiling of peripheral CD45RA+ and CD45RO+CD4+CD25+CD127(low) Treg cells in sufferers with power rheumatoid arthritis. Arthritis Rheumatol. 68, 103–116 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Seddiki, N. et al. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 203, 1693–1700 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nakagawa, H. et al. Instability of Helios-deficient Tregs is related to conversion to a T-effector phenotype and enhanced antitumor immunity. Proc. Natl. Acad. Sci. USA. 113, 6248–6253 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lam, A. J., Uday, P., Gillies, J. Okay. & Levings, M. Okay. Helios is a marker, not a driver, of human Treg stability. Eur. J. Immunol. 52, 75–84 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Takatori, H. et al. Helios enhances Treg cell operate in cooperation with FoxP3. Arthritis Rheumatol. 67, 1491–1502 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim, H. J. et al. Secure inhibitory exercise of regulatory T cells requires the transcription issue Helios. Science 350, 334–339 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Piersiala, Okay. et al. Tumour-draining lymph nodes in head and neck most cancers are characterised by accumulation of CTLA-4 and PD-1 expressing Treg cells. Transl. Oncol. 23, 101469 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ohkura, N. & Sakaguchi, S. Transcriptional and epigenetic foundation of Treg cell improvement and performance: its genetic anomalies or variations in autoimmune ailments. Cell Res. 30, 465–474 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mitsuiki, N., Schwab, C. & Grimbacher, B. What did we be taught from CTLA-4 insufficiency on the human immune system? Immunol. Rev. 287, 33–49 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Diamantopoulos, N. et al. ICOS-expressing regulatory T cells affect the composition of antitumor CTL populations. J. Immunol. 213, 753–762 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yan, F. et al. Prognostic and therapeutic potential of imbalance between PD-1+CD8 and ICOS+Treg cells in superior HBV-HCC. Most cancers Sci. 115, 2553–2564 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, D. Y. & Xiong, X. Z. ICOS(+) Tregs: a useful subset of Tregs in immune ailments. Entrance. Immunol. 11, 2104 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jin, X. et al. Use of Tregs as a cell-based remedy by way of CD39 for benign prostate hyperplasia with irritation. J. Cell. Mol. Med. 24, 5082–5096 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, C. et al. CD39(+) regulatory T cells attenuate lipopolysaccharide-induced acute lung damage by way of autophagy and the ERK/FOS pathway. Entrance. Immunol. 11, 602605 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • He, J. et al. TNFR2-expressing CD4(+)Foxp3(+) regulatory T cells in most cancers immunology and immunotherapy. Prog. Mol. Biol. Transl. Sci. 164, 101–117 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Abi-Aad, S. J. et al. Simultaneous inhibition of PD-1 and LAG-3: the way forward for immunotherapy? Immunotherapy 15, 611–618 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Opstelten, R. et al. GPA33: a marker to determine steady human regulatory T cells. J. Immunol. 204, 3139–3148 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhao, Y. et al. Alterations in Helios+ T cell subsets in peripheral blood of early-stage lung adenocarcinoma sufferers: implications for early prognosis. Immunobiology 228, 152749 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Opstelten, R. et al. GPA33 is expressed on a number of human blood cell sorts and distinguishes CD4(+) central reminiscence T cells with and with out effector operate. Eur. J. Immunol. 51, 1377–1389 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mensink, M. et al. TNFR2 costimulation differentially impacts regulatory and standard CD4(+) T-cell metabolism. Entrance. Immunol. 13, 881166 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cantor, H. et al. Immunoregulatory circuits amongst T-cell units. II. Physiologic function of suggestions inhibition in vivo: absence in NZB mice. J. Exp. Med. 147, 1116–1125 (1978).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jiang, H., Zhang, S. I. & Pernis, B. Function of CD8+T cells in murine experimental allergic encephalomyelitis. Science 256, 1213–1215 (1992).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, J. et al. KIR(+)CD8(+) T cells suppress pathogenic T cells and are energetic in autoimmune ailments and COVID-19. Science 376, eabi9591 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Churlaud, G. et al. Human and mouse CD8+CD25+FOXP3+ regulatory T cells at regular state and through interleukin-2 remedy. Entrance. Immunol. 6, 171 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Robb, R. J. et al. Identification and growth of extremely suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation. Blood 119, 5898–5908 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Joeris, T. et al. Intestinal cDC1 drive cross-tolerance to epithelial-derived antigen by way of induction of FoxP3+CD Tregs. Sci. Immunol. 6, eabd3774 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vuttaradhi, V. Okay. et al. CD8+ regulatory T cells. Annu. Rev. Immunol. 44, 21–40 (2026).

  • Kim, H. J. et al. Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is crucial for self tolerance. Nature 467, 328–332 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, H. J. et al. CD8+T regulatory cells categorical the Ly49 Class I MHC receptor and are faulty in autoimmune susceptible B6-Yaa mice. Proc. Natl. Acad. Sci. USA. 108, 2010–2015 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saligrama, N. et al. Opposing T cell responses in experimental autoimmune encephalomyelitis. Nature 572, 481–487 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, J. et al. Regulatory KIR(+)CD8(+) T cells are elevated throughout human being pregnant. Sci. Transl. Med. 17, eadm7697 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, X. et al. Differential roles of human CD4(+) and CD8(+) regulatory T cells in controlling self-reactive immune responses. Nat. Immunol. 26, 230–239 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Niebel, D. et al. Cutaneous lupus erythematosus: an replace on pathogenesis and future therapeutic instructions. Am. J. Clin. Dermatol. 24, 521–540 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lim, C. C. et al. Extreme infections in sufferers with lupus nephritis handled with immunosuppressants: a retrospective cohort examine. Nephrology 22, 478–484 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fairfield, C. et al. Glucocorticosteroid-free versus glucocorticosteroid-containing immunosuppression for liver transplanted sufferers. Cochrane Database Syst. Rev. 4, Cd007606 (2018).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mikami, N. et al. Producing functionally steady and antigen-specific T(reg) cells from effector T cells for cell remedy of inflammatory ailments. Sci. Transl. Med. 17, eadr6049 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mukai, M. et al. Conversion of pathogenic T cells into functionally stabilized T(reg) cells for antigen-specific immunosuppression in pemphigus vulgaris. Sci. Transl. Med. 17, eadq9913 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lio, C. W. & Hsieh, C. S. A two-step course of for thymic regulatory T cell improvement. Immunity 28, 100–111 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Klein, L., Kyewski, B., Allen, P. M. & Hogquist, Okay. A. Constructive and unfavourable number of the T cell repertoire: what thymocytes see (and don’t see). Nat. Rev. Immunol. 14, 377–391 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aschenbrenner, Okay. et al. Number of Foxp3+ regulatory T cells particular for self antigen expressed and introduced by Aire+ medullary thymic epithelial cells. Nat. Immunol. 8, 351–358 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Leventhal, D. S. et al. Dendritic cells coordinate the event and homeostasis of organ-specific regulatory T cells. Immunity 44, 847–859 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Perry, J. S. A. et al. Distinct contributions of Aire and antigen-presenting-cell subsets to the era of self-tolerance within the thymus. Immunity 41, 414–426 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, M. O. & Rudensky, A. Y. T cell receptor signalling within the management of regulatory T cell differentiation and performance. Nat. Rev. Immunol. 16, 220–233 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Barnes, M. J. et al. Dedication to the regulatory T cell lineage requires CARMA1 within the thymus however not within the periphery. PLoS Biol. 7, e51 (2009).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Medoff, B. D. et al. Differential requirement for CARMA1 in agonist-selected T-cell improvement. Eur. J. Immunol. 39, 78–84 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tone, Y. et al. Smad3 and NFAT cooperate to induce Foxp3 expression via its enhancer. Nat. Immunol. 9, 194–202 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Josefowicz, S. Z., Lu, L. F. & Rudensky, A. Y. Regulatory T cells: mechanisms of differentiation and performance. Annu. Rev. Immunol. 30, 531–564 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tanaka, A. et al. Development of a T cell receptor signaling vary for spontaneous improvement of autoimmune illness. J. Exp. Med. 220, e20220386 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sauer, S. et al. T cell receptor signaling controls Foxp3 expression by way of PI3K, Akt, and mTOR. Proc. Natl. Acad. Sci. USA. 105, 7797–7802 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Watanabe, M., Lu, Y., Breen, M. & Hodes, R. J. B7-CD28 co-stimulation modulates central tolerance by way of thymic clonal deletion and Treg era via distinct mechanisms. Nat. Commun. 11, 6264 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tai, X., Cowan, M., Feigenbaum, L. & Singer, A. CD28 costimulation of creating thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2. Nat. Immunol. 6, 152–162 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Caramalho, I. et al. Human regulatory T-cell improvement is dictated by Interleukin-2 and -15 expressed in a non-overlapping sample within the thymus. J. Autoimmun. 56, 98–110 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Harris, F., Berdugo, Y. A. & Tree, T. IL-2-based approaches to Treg enhancement. Clin. Exp. Immunol. 211, 149–163 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kumar, P. et al. Essential function of OX40 signaling within the TCR-independent part of human and murine thymic Treg era. Cell. Mol. Immunol. 16, 138–153 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Apert, C., Romagnoli, P. & van Meerwijk, J. P. M. IL-2 and IL-15 dependent thymic improvement of Foxp3-expressing regulatory T lymphocytes. Protein Cell 9, 322–332 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Apert, C. et al. IL-2 and IL-15 drive intrathymic improvement of distinct periphery-seeding CD4(+)Foxp3(+) regulatory T lymphocytes. Entrance. Immunol. 13, 965303 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yoshie, O. & Matsushima, Okay. CCR4 and its ligands: from bench to bedside. Int. Immunol. 27, 11–20 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Thiault, N. et al. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the event of their precursors. Nat. Immunol. 16, 628–634 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cowan, J. E., McCarthy, N. I. & Anderson, G. CCR7 controls thymus recirculation, however not manufacturing and emigration, of Foxp3(+) T cells. Cell Rep. 14, 1041–1048 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nikolouli, E. et al. Recirculating IL-1R2(+) Tregs fine-tune intrathymic Treg improvement beneath inflammatory circumstances. Cell. Mol. Immunol. 18, 182–193 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Peters, V. A., Joesting, J. J. & Freund, G. G. IL-1 receptor 2 (IL-1R2) and its function in immune regulation. Mind Behav. Immun. 32, 1–8 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wesa, A. & Galy, A. Elevated manufacturing of pro-inflammatory cytokines and enhanced T cell responses after activation of human dendritic cells with IL-1 and CD40 ligand. BMC Immunol. 3, 14 (2002).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Korn, T. et al. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of standard T cells into Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. USA. 105, 18460–18465 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lemarquis, A. L. et al. Recirculating regulatory T cells mediate thymic regeneration via amphiregulin following injury. Immunity 58, 397–411.e396 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Levine, A. G., Arvey, A., Jin, W. & Rudensky, A. Y. Steady requirement for the TCR in regulatory T cell operate. Nat. Immunol. 15, 1070–1078 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lathrop, S. Okay. et al. Peripheral training of the immune system by colonic commensal microbiota. Nature 478, 250–254 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hsieh, C. S. et al. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat. Immunol. 7, 401–410 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yeste, A. et al. Tolerogenic nanoparticles inhibit T cell–mediated autoimmunity via SOCS2. Sci. Sign. 9, ra61–ra61 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Krienke, C. et al. A noninflammatory mRNA vaccine for therapy of experimental autoimmune encephalomyelitis. Science 371, 145–153 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Scurlock, A. M. & Jones, S. M. An replace on immunotherapy for meals allergy. Curr. Opin. Allergy Clin. Immunol. 10, 587–593 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lengthy, S. A. et al. Low-dose antigen promotes induction of FOXP3 in human CD4+T cells. J. Immunol. 187, 3511–3520 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Whibley, N., Tucci, A. & Powrie, F. Regulatory T cell adaptation within the gut and pores and skin. Nat. Immunol. 20, 386–396 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim, Okay. S. et al. Dietary antigens restrict mucosal immunity by inducing regulatory T cells within the small gut. Science 351, 858–863 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Syed, A. et al. Peanut oral immunotherapy leads to elevated antigen-induced regulatory T-cell operate and hypomethylation of forkhead field protein 3 (FOXP3). J. Allergy Clin. Immunol. 133, 500–510 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vickery, B. P. et al. Sustained unresponsiveness to peanut in topics who’ve accomplished peanut oral immunotherapy. J. Allergy Clin. Immunol. 133, 468–475 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Takasato, Y. et al. Orally desensitized mast cells kind a regulatory community with Treg cells for the management of meals allergy. Mucosal Immunol. 14, 640–651 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lozano-Ojalvo, D. et al. Allergen recognition by particular effector Th2 cells permits IL-2-dependent activation of regulatory T-cell responses in people. Allergy 78, 697–713 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Setoguchi, R., Hori, S., Takahashi, T. & Sakaguchi, S. Homeostatic upkeep of pure Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune illness by IL-2 neutralization. J. Exp. Med. 201, 723–735 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liao, W., Lin, J. X. & Leonard, W. J. Interleukin-2 on the crossroads of effector responses, tolerance, and immunotherapy. Immunity 38, 13–25 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Miyazaki, T. et al. Purposeful activation of Jak1 and Jak3 by selective affiliation with IL-2 receptor subunits. Science 266, 1045–1047 (1994).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Beadling, C. et al. Activation of JAK kinases and STAT proteins by interleukin-2 and interferon alpha, however not the T cell antigen receptor, in human T lymphocytes. EMBO J. 13, 5605–5615 (1994).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ross, S. H. & Cantrell, D. A. Signaling and performance of interleukin-2 in T lymphocytes. Annu. Rev. Immunol. 36, 411–433 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Solar, H. et al. IL-2 can sign by way of chemokine receptors to advertise regulatory T cells’ suppressive operate. Cell Rep. 42, 112996 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Setiady, Y. Y., Coccia, J. A. & Park, P. U. In vivo depletion of CD4+FOXP3+ Treg cells by the PC61 anti-CD25 monoclonal antibody is mediated by FcgammaRIII+ phagocytes. Eur. J. Immunol. 40, 780–786 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Abbas, A. Okay. et al. Revisiting IL-2: biology and therapeutic prospects. Sci. Immunol. 3, eaat1482 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Arenas-Ramirez, N., Woytschak, J. & Boyman, O. Interleukin-2: biology, design and utility. Developments Immunol. 36, 763–777 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Trotta, E. et al. A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism. Nat. Med. 24, 1005–1014 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yu, A. et al. Selective IL-2 responsiveness of regulatory T cells via a number of intrinsic mechanisms helps using low-dose IL-2 remedy in sort 1 diabetes. Diabetes 64, 2172–2183 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tang, Q. et al. Central function of faulty interleukin-2 manufacturing within the triggering of islet autoimmune destruction. Immunity 28, 687–697 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Konrad, M. W. et al. Pharmacokinetics of recombinant interleukin 2 in people. Most cancers Res. 50, 2009–2017 (1990).

    CAS 
    PubMed 

    Google Scholar
     

  • Service provider, R. et al. Tremendous-tuned long-acting interleukin-2 superkine potentiates sturdy immune responses in mice and non-human primate. J. Immunother. Most cancers 10, e003155 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lengthy, S. A. et al. Rapamycin/IL-2 mixture remedy in sufferers with sort 1 diabetes augments Tregs but transiently impairs β-cell operate. Diabetes 61, 2340–2348 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Spangler, J. B. et al. Antibodies to interleukin-2 elicit selective T cell subset potentiation via distinct conformational mechanisms. Immunity 42, 815–825 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pilat, N. et al. Treg-mediated extended survival of pores and skin allografts with out immunosuppression. Proc. Natl. Acad. Sci. USA. 116, 13508–13516 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Khoryati, L. et al. An IL-2 mutein engineered to advertise growth of regulatory T cells arrests ongoing autoimmunity in mice. Sci. Immunol. 5, eaba5264 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Music, Q. et al. Tolerogenic anti-IL-2 mAb prevents graft-versus-host illness whereas preserving robust graft-versus-leukemia exercise. Blood 137, 2243–2255 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • VanDyke, D. et al. Engineered human cytokine/antibody fusion proteins develop regulatory T cells and confer autoimmune illness safety. Cell Rep. 41, 111478 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Peterson, L. B. et al. A protracted-lived IL-2 mutein that selectively prompts and expands regulatory T cells as a remedy for autoimmune illness. J. Autoimmun. 95, 1–14 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ghelani, A. et al. Defining the edge IL-2 sign required for induction of selective Treg cell responses utilizing engineered IL-2 muteins. Entrance. Immunol. 11, 1106 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jamison, B. L. et al. An IL-2 mutein will increase regulatory T cell suppression of dendritic cells by way of IL-10 and CTLA-4 to advertise T cell anergy. Cell Rep. 43, 114938 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Efe, O. et al. A humanized IL-2 mutein expands Tregs and prolongs transplant survival in preclinical fashions. J. Clin. Make investments. 134, e173107 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, M. O. et al. Reworking progress factor-beta regulation of immune responses. Annu. Rev. Immunol. 24, 99–146 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, J., Zhao, X. & Wan, Y. Y. Intricacies of TGF-β signaling in Treg and Th17 cell biology. Cell. Mol. Immunol. 20, 1002–1022 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Marie, J. C., Letterio, J. J., Gavin, M. & Rudensky, A. Y. TGF-beta1 maintains suppressor operate and Foxp3 expression in CD4+CD25+ regulatory T cells. J. Exp. Med. 201, 1061–1067 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tang, N. et al. TGF-β inhibition by way of CRISPR promotes the long-term efficacy of CAR T cells towards strong tumors. JCI Perception 5, e133977 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kanamori, M. et al. Induced regulatory T cells: their improvement, stability, and purposes. Developments Immunol. 37, 803–811 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zheng, Y. et al. Function of conserved non-coding DNA parts within the Foxp3 gene in regulatory T-cell destiny. Nature 463, 808–812 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ouyang, W., Beckett, O., Ma, Q. & Li, M. O. Reworking progress factor-beta signaling curbs thymic unfavourable choice selling regulatory T cell improvement. Immunity 32, 642–653 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Konkel, J. E. et al. Management of the event of CD8αα+ intestinal intraepithelial lymphocytes by TGF-β. Nat. Immunol. 12, 312–319 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fang, Y. et al. Mitochondrial fusion induced by reworking progress factor-β1 serves as a swap that governs the metabolic reprogramming throughout differentiation of regulatory T cells. Redox Biol. 62, 102709 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Koprivica, I. et al. Orally delivered all-trans-retinoic acid- and reworking progress factor-β-loaded microparticles ameliorate sort 1 diabetes in mice. Eur. J. Pharmacol. 864, 172721 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Elias, Okay. M. et al. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression via a Stat-3/Stat-5 unbiased signaling pathway. Blood 111, 1013–1020 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mucida, D. et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317, 256–260 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, W. & Ten Dijke, P. Immunoregulation by members of the TGFβ superfamily. Nat. Rev. Immunol. 16, 723–740 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • York, A. G. et al. IL-10 constrains sphingolipid metabolism to restrict irritation. Nature 627, 628–635 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chaudhry, A. et al. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated irritation. Immunity 34, 566–578 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shouval, D. S. et al. Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti inflammatory macrophage operate. Immunity 40, 706–719 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Music, J. et al. MiR-192-5p/RB1/NF-κBp65 signaling axis promotes IL-10 secretion throughout gastric most cancers EMT to induce Treg cell differentiation within the tumour microenvironment. Clin. Transl. Med. 12, e992 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Laragione, T. et al. Magnesium will increase numbers of Foxp3+ Treg cells and reduces arthritis severity and joint injury in an IL-10-dependent method mediated by the intestinal microbiome. EBioMedicine 92, 104603 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Prodjinotho, U. F. et al. Helminthic dehydrogenase drives PGE(2) and IL-10 manufacturing in monocytes to potentiate Treg induction. EMBO Rep. 23, e54096 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hsu, P. et al. IL-10 potentiates differentiation of human induced regulatory T cells by way of STAT3 and Foxo1. J. Immunol. 195, 3665–3674 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ouyang, W. et al. Novel Foxo1-dependent transcriptional packages management T(reg) cell operate. Nature 491, 554–559 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, X. et al. RNF213 promotes Treg cell differentiation by facilitating K63-linked ubiquitination and nuclear translocation of FOXO1. Nat. Commun. 15, 5961 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ouyang, W. et al. Foxo proteins cooperatively management the differentiation of Foxp3+ regulatory T cells. Nat. Immunol. 11, 618–627 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kerdiles, Y. M. et al. Foxo transcription components management regulatory T cell improvement and performance. Immunity 33, 890–904 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Collison, L. W. et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell operate. Nature 450, 566–569 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Collison, L. W. et al. The composition and signaling of the IL-35 receptor are unconventional. Nat. Immunol. 13, 290–299 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shao, Y. et al. IL-35 promotes CD4+Foxp3+ Tregs and inhibits atherosclerosis by way of sustaining CCR5-amplified Treg-suppressive mechanisms. JCI Perception 6, e152511 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rhodes, Okay. R. et al. Bioengineered particles develop myelin-specific regulatory T cells and reverse autoreactivity in a mouse mannequin of a number of sclerosis. Sci. Adv. 9, eadd8693 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mikami, N. et al. Epigenetic conversion of standard T cells into regulatory T cells by CD28 sign deprivation. Proc. Natl. Acad. Sci. USA. 117, 12258–12268 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ohkura, N. et al. T cell receptor stimulation-induced epigenetic modifications and Foxp3 expression are unbiased and complementary occasions required for Treg cell improvement. Immunity 37, 785–799 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chi, H. Regulation and performance of mTOR signalling in T cell destiny selections. Nat. Rev. Immunol. 12, 325–338 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, Okay. Regulation of Treg cell metabolism and performance in non-lymphoid tissues. Entrance. Immunol. 13, 909705 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shi, L. Z. et al. HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells. J. Exp. Med. 208, 1367–1376 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Layman, A. A. Okay. et al. Ndfip1 restricts mTORC1 signalling and glycolysis in regulatory T cells to forestall autoinflammatory illness. Nat. Commun. 8, 15677 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Park, Y. et al. TSC1 regulates the steadiness between effector and regulatory T cells. J. Clin. Make investments. 123, 5165–5178 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shrestha, S. et al. Treg cells require the phosphatase PTEN to restrain TH1 and TFH cell responses. Nat. Immunol. 16, 178–187 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Powell, J. D., Pollizzi, Okay. N., Heikamp, E. B. & Horton, M. R. Regulation of immune responses by mTOR. Annu. Rev. Immunol. 30, 39–68 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Merkenschlager, M. & von Boehmer, H. PI3 kinase signalling blocks Foxp3 expression by sequestering Foxo components. J. Exp. Med. 207, 1347–1350 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Procaccini, C. et al. An oscillatory swap in mTOR kinase exercise units regulatory T cell responsiveness. Immunity 33, 929–941 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, J. H., Lydon, J. P. & Kim, C. H. Progesterone suppresses the mTOR pathway and promotes era of induced regulatory T cells with elevated stability. Eur. J. Immunol. 42, 2683–2696 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Newton, R., Priyadharshini, B. & Turka, L. A. Immunometabolism of regulatory T cells. Nat. Immunol. 17, 618–625 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huynh, A. et al. Management of PI(3) kinase in Treg cells maintains homeostasis and lineage stability. Nat. Immunol. 16, 188–196 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zeng, H. et al. mTORC1 {couples} immune alerts and metabolic programming to ascertain T(reg)-cell operate. Nature 499, 485–490 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shackelford, D. B. & Shaw, R. J. The LKB1-AMPK pathway: metabolism and progress management in tumour suppression. Nat. Rev. Most cancers 9, 563–575 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, D. et al. Lkb1 maintains T(reg) cell lineage identification. Nat. Commun. 8, 15876 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Campesato, L. F. et al. Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine. Nat. Commun. 11, 4011 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cheong, J. E. & Solar, L. Focusing on the IDO1/TDO2-KYN-AhR pathway for most cancers immunotherapy – challenges and alternatives. Developments Pharmacol. Sci. 39, 307–325 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, Q. et al. AhR activation promotes Treg cell era by enhancing Lkb1-mediated fatty acid oxidation by way of the Skp2/K63-ubiquitination pathway. Immunology 169, 412–430 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • He, N. et al. Metabolic management of regulatory T cell (Treg) survival and performance by Lkb1. Proc. Natl. Acad. Sci. USA. 114, 12542–12547 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, X. et al. Zfp335 establishes eTreg lineage and neonatal immune tolerance by focusing on Hadha-mediated fatty acid oxidation. J. Clin. Make investments. 133, e166628 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Timilshina, M. et al. Activation of mevalonate pathway by way of LKB1 is crucial for stability of T(reg) cells. Cell Rep. 27, 2948–2961.e2947 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, Y., Zhang, J., Cui, W. & Silverstein, R. L. CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and destiny. J. Exp. Med. 219, e20211314 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Leduc, V., Jasmin-Bélanger, S. & Poirier, J. APOE and ldl cholesterol homeostasis in Alzheimer’s illness. Developments Mol. Med. 16, 469–477 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, H. et al. Intestine microbial metabolites in inflammatory bowel illness: immunological mechanisms regulating Treg/Th17 steadiness and therapeutic potential. Entrance Immunol. 17, 1780865 (2026).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brown, J. A. et al. Intestine microbiota promotes immune tolerance on the maternal-fetal interface. Cell 189, 196–214.e124 (2026).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, B. et al. Tryptophan catabolites from microbiota ameliorate immune-mediated hepatitis via activating aryl hydrocarbon receptor of T cells. Intestine Microbes 17, 2557979 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yan, Y. et al. Metabolic profiles of regulatory T cells and their variations to the tumor microenvironment: implications for antitumor immunity. J. Hematol. Oncol. 15, 104 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Watson, M. J. et al. Metabolic assist of tumour-infiltrating regulatory T cells by lactic acid. Nature 591, 645–651 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kumagai, S. et al. Lactic acid promotes PD-1 expression in regulatory T cells in extremely glycolytic tumor microenvironments. Most cancers Cell 40, 201–218.e209 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tuomela, Okay. et al. Lactic acid improves Treg manufacturing and in vivo operate. Mol. Ther. Strategies Clin. Dev. 33, 101600 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Koenecke, C. et al. Alloantigen-specific de novo-induced Foxp3+ Treg revert in vivo and don’t shield from experimental GVHD. Eur. J. Immunol. 39, 3091–3096 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, J. et al. Management of Foxp3 induction and upkeep by sequential histone acetylation and DNA demethylation. Cell Rep. 37, 110124 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Polansky, J. Okay. et al. Methylation issues: binding of Ets-1 to the demethylated Foxp3 gene contributes to the stabilization of Foxp3 expression in regulatory T cells. J. Mol. Med. 88, 1029–1040 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Iizuka-Koga, M. et al. Induction and upkeep of regulatory T cells by transcription components and epigenetic modifications. J. Autoimmun. 83, 113–121 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vaeth, M. et al. Dependence on nuclear issue of activated T-cells (NFAT) ranges discriminates standard T cells from Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. USA. 109, 16258–16263 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arroyo-Olarte, R. D. et al. Focused demethylation of FOXP3-TSDR enhances the suppressive capability of STAT6-deficient inducible T regulatory cells. Irritation 47, 2159–2172 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, R. et al. Hydrogen sulfide promotes Tet1- and Tet2-mediated Foxp3 demethylation to drive regulatory T cell differentiation and keep immune homeostasis. Immunity 43, 251–263 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kohli, R. M. & Zhang, Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature 502, 472–479 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Music, S. J. et al. MicroRNA-antagonism regulates breast most cancers stemness and metastasis by way of TET-family-dependent chromatin reworking. Cell 154, 311–324 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yue, X. et al. Management of Foxp3 stability via modulation of TET exercise. J. Exp. Med. 213, 377–397 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yue, X. et al. Entire-genome evaluation of TET dioxygenase operate in regulatory T cells. EMBO Rep. 22, e52716 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wakamatsu, E. et al. Sturdy TCR stimulation promotes the stabilization of Foxp3 expression in regulatory T cells induced in vitro via growing the demethylation of Foxp3 CNS2. Biochem. Biophys. Res. Commun. 503, 2597–2602 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Takaki, H. et al. STAT6 Inhibits TGF-beta1-mediated Foxp3 induction via direct binding to the Foxp3 promoter, which is reverted by retinoic acid receptor. J. Biol. Chem. 283, 14955–14962 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arroyo-Olarte, R. D. et al. STAT6 controls the soundness and suppressive operate of regulatory T cells. Eur. J. Immunol. 53, e2250128 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Cameron, J., Martino, P., Nguyen, L. & Li, X. Innovative: CRISPR-based transcriptional regulators reveal transcription-dependent institution of epigenetic reminiscence of Foxp3 in regulatory T cells. J. Immunol. 205, 2953–2958 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xiao, Y. et al. Histone acetyltransferase mediated regulation of FOXP3 acetylation and Treg operate. Curr. Opin. Immunol. 22, 583–591 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Haberland, M., Montgomery, R. L. & Olson, E. N. The various roles of histone deacetylases in improvement and physiology: implications for illness and remedy. Nat. Rev. Genet 10, 32–42 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tao, R. et al. Deacetylase inhibition promotes the era and performance of regulatory T cells. Nat. Med. 13, 1299–1307 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Castillo, J. et al. CBP/p300 drives the differentiation of regulatory T cells via transcriptional and non-transcriptional mechanisms. Most cancers Res. 79, 3916–3927 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, Q. et al. Histone acetyltransferases CBP/p300 in tumorigenesis and CBP/p300 inhibitors as promising novel anticancer brokers. Theranostics 12, 4935–4948 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, Y. et al. Inhibition of p300 impairs Foxp3⁺ T regulatory cell operate and promotes antitumor immunity. Nat. Med. 19, 1173–1177 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, Y. et al. Two histone/protein acetyltransferases, CBP and p300, are indispensable for Foxp3+ T-regulatory cell improvement and performance. Mol. Cell Biol. 34, 3993–4007 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dong, Y., Yang, C. & Pan, F. Publish-translational laws of Foxp3 in Treg cells and their therapeutic purposes. Entrance. Immunol. 12, 626172 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, L. et al. Constructive and unfavourable transcriptional regulation of the Foxp3 gene is mediated by entry and binding of the Smad3 protein to enhancer I. Immunity 33, 313–325 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ma, Z. et al. Regulatory roles of intestinal CD4(+) T cells in irritation and their modulation by the intestinal microbiota. Intestine Microbes 17, 2560019 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arpaia, N. et al. Metabolites produced by commensal micro organism promote peripheral regulatory T-cell era. Nature 504, 451–455 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, L. et al. Microbiome-metabolome generated bile acids gatekeep infliximab efficacy in Crohn’s illness by licensing M1 suppression and Treg dominance. J. Adv. Res. 83, 789–806 (2026).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cling, S. et al. Bile acid metabolites management TH17 and Treg cell differentiation. Nature 576, 143–148 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, W. et al. A bacterial bile acid metabolite modulates T(reg) exercise via the nuclear hormone receptor NR4A1. Cell Host Microbe 29, 1366–1377.e1369 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kong, Y. et al. CAR-T cell remedy: developments, challenges and expanded purposes from most cancers to autoimmunity. Entrance. Immunol. 15, 1519671 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sterner, R. C. & Sterner, R. M. CAR-T cell remedy: present limitations and potential methods. Blood Most cancers J. 11, 69 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fritsche, E., Volk, H. D., Reinke, P. & Abou-El-Enein, M. Towards an optimized course of for scientific manufacturing of CAR-Treg cell remedy. Developments Biotechnol. 38, 1099–1112 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Barra, J. M. et al. Combinatorial genetic engineering technique for immune safety of stem cell-derived beta cells by chimeric antigen receptor regulatory T cells. Cell Rep. 43, 114994 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Muller, Y. D. et al. Precision engineering of an Anti-HLA-A2 chimeric antigen receptor in regulatory T cells for transplant immune tolerance. Entrance. Immunol. 12, 686439 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Eskandari, S. Okay., Daccache, A. & Azzi, J. R. Chimeric antigen receptor T(reg) remedy in transplantation. Developments Immunol. 45, 48–61 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • MacDonald, Okay. G. et al. Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. J. Clin. Make investments. 126, 1413–1424 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Boardman, D. A. et al. Flagellin-specific human CAR Tregs for immune regulation in IBD. J. Autoimmun. 134, 102961 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Frikeche, J. et al. MOG-specific CAR Tregs: a novel method to deal with a number of sclerosis. J. Neuroinflammation 21, 268 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Spanier, J. A. et al. Tregs with an MHC class II peptide-specific chimeric antigen receptor forestall autoimmune diabetes in mice. J. Clin. Make investments. 133, e168601 (2023).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arjomandnejad, M., Kopec, A. L. & Keeler, A. M. CAR-T regulatory (CAR-Treg) cells: engineering and purposes. Biomedicines 10, 287 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fransson, M. et al. CAR/FoxP3-engineered T regulatory cells goal the CNS and suppress EAE upon intranasal supply. J. Neuroinflammation 9, 112 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Solar, N. et al. Nanoneedle-based electroporation for environment friendly manufacturing of human main chimeric antigen receptor regulatory T-cells. Adv. Sci. 12, e2416066 (2025).

    Article 

    Google Scholar
     

  • Bacher, P. et al. Regulatory T cell specificity directs tolerance versus allergy towards aeroantigens in people. Cell 167, 1067–1078.e1016 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Boroughs, A. C. et al. Chimeric antigen receptor costimulation domains modulate human regulatory T cell operate. JCI Perception 5, e126194 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lamarche, C. et al. Tonic-signaling chimeric antigen receptors drive human regulatory T cell exhaustion. Proc. Natl. Acad. Sci. USA. 120, e2219086120 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lamarthée, B. et al. Transient mTOR inhibition rescues 4-1BB CAR-Tregs from tonic signal-induced dysfunction. Nat. Commun. 12, 6446 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Doglio, M. et al. Regulatory T cells expressing CD19-targeted chimeric antigen receptor restore homeostasis in Systemic Lupus Erythematosus. Nat. Commun. 15, 2542 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cochrane, R. W. et al. Excessive-affinity chimeric antigen receptor signaling induces an inflammatory program in human regulatory T cells. Mol. Ther. Strategies Clin. Dev. 32, 101385 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grauwet, Okay. et al. Stealth transgenes allow CAR-T cells to evade host immune responses. J. Immunother. Most cancers 12, e008417 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wagner, D. L. et al. Immunogenicity of CAR T cells in most cancers remedy. Nat. Rev. Clin. Oncol. 18, 379–393 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Blat, D. et al. Suppression of murine colitis and its related most cancers by carcinoembryonic antigen-specific regulatory T cells. Mol. Ther. 22, 1018–1028 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wendering, D. J. et al. The worth of a fast check of human regulatory T cell operate must be revised. Entrance. Immunol. 10, 150 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sakaguchi, S., Yamaguchi, T., Nomura, T. & Ono, M. Regulatory T cells and immune tolerance. Cell 133, 775–787 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Göschl, L., Scheinecker, C. & Bonelli, M. Treg cells in autoimmunity: from identification to Treg-based therapies. Semin. Immunopathol. 41, 301–314 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Tanaka, A. & Sakaguchi, S. Focusing on Treg cells in most cancers immunotherapy. Eur. J. Immunol. 49, 1140–1146 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hasenkrug, Okay. J., Chougnet, C. A. & Dittmer, U. Regulatory T cells in retroviral infections. PLoS Pathog. 14, e1006776 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chi, X. et al. Innate and adaptive immune abnormalities underlying autoimmune ailments: the genetic connections. Sci. China Life Sci. 66, 1482–1517 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grey, P. E. & David, C. Inborn errors of immunity and autoimmune illness. J. Allergy Clin. Immunol. Pract. 11, 1602–1622 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Torres-Aguilar, H., Sosa-Luis, S. A. & Aguilar-Ruiz, S. R. Infections as triggers of flares in systemic autoimmune ailments: novel innate immunity mechanisms. Curr. Opin. Rheumatol. 31, 525–531 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cleaver, J. et al. The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity. Mind 147, 1130–1148 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wagner, A. et al. Metabolic modeling of single Th17 cells reveals regulators of autoimmunity. Cell 184, 4168–4185.e4121 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aso, Okay. et al. Itaconate ameliorates autoimmunity by modulating T cell imbalance by way of metabolic and epigenetic reprogramming. Nat. Commun. 14, 984 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shakya, A. Okay. & Nandakumar, Okay. S. Antigen-specific tolerization and focused supply as therapeutic methods for autoimmune ailments. Developments Biotechnol. 36, 686–699 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kiriakidou, M. & Ching, C. L. Systemic lupus erythematosus. Ann. Intern. Med. 172, Itc81–itc96 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Hoi, A., Igel, T., Mok, C. C. & Arnaud, L. Systemic lupus erythematosus. Lancet 403, 2326–2338 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bluestone, J. A., Bour-Jordan, H., Cheng, M. & Anderson, M. T cells within the management of organ-specific autoimmunity. J. Clin. Make investments. 125, 2250–2260 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, J. et al. Imbalance of Th17 cells, Treg cells and related cytokines in sufferers with systemic lupus erythematosus: a meta-analysis. Entrance. Immunol. 15, 1425847 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bonelli, M., Smolen, J. S. & Scheinecker, C. Treg and lupus. Ann. Rheum. Dis. 69, i65–i66 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dao, L. T. M. et al. Present cell therapies for systemic lupus erythematosus. Stem Cells Transl. Med. 13, 859–872 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chuang, H. C. et al. BPI overexpression suppresses Treg differentiation and induces exosome-mediated irritation in systemic lupus erythematosus. Theranostics 11, 9953–9966 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Makita, S. et al. RNA-binding protein ZFP36L2 downregulates helios expression and suppresses the operate of regulatory T cells. Entrance. Immunol. 11, 1291 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • von Spee-Mayer, C. et al. Low-dose interleukin-2 selectively corrects regulatory T cell defects in sufferers with systemic lupus erythematosus. Ann. Rheum. Dis. 75, 1407–1415 (2016).

    Article 

    Google Scholar
     

  • Humrich, J. Y. et al. Low-dose interleukin-2 remedy in energetic systemic lupus erythematosus (LUPIL-2): a multicentre, double-blind, randomised and placebo-controlled part II trial. Ann. Rheum. Dis. 81, 1685–1694 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Raeber, M. E. et al. Interleukin-2 immunotherapy reveals human regulatory T cell subsets with distinct useful and tissue-homing traits. Immunity 57, 2232–2250.e2210 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Miao, M. et al. Therapeutic potential of focusing on Tfr/Tfh cell steadiness by low-dose-IL-2 in energetic SLE: a put up hoc evaluation from a double-blind RCT examine. Arthritis Res. Ther. 23, 167 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Humrich, J. Y. et al. Fast induction of scientific remission by low-dose interleukin-2 in a affected person with refractory SLE. Ann. Rheum. Dis. 74, 791–792 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Zhao, C. et al. Low dose of IL-2 mixed with rapamycin restores and maintains the long-term steadiness of Th17/Treg cells in refractory SLE sufferers. BMC Immunol. 20, 32 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ilonen, J., Lempainen, J. & Veijola, R. The heterogeneous pathogenesis of sort 1 diabetes mellitus. Nat. Rev. Endocrinol. 15, 635–650 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ben-Skowronek, I. et al. Potential therapeutic utility of regulatory T cells in diabetes mellitus sort 1. Int. J. Mol. Sci. 23, 390 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, Y. F. et al. Immune and metabolic results of antigen-specific immunotherapy utilizing a number of β-cell peptides in sort 1. Diabetes Diabetes 71, 722–732 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Scherm, M. G. et al. miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in fashions of sort 1 diabetes. Nat. Commun. 10, 5697 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Serr, I. et al. Kind 1 diabetes vaccine candidates promote human Foxp3(+)Treg induction in humanized mice. Nat. Commun. 7, 10991 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bluestone, J. A. et al. Kind 1 diabetes immunotherapy utilizing polyclonal regulatory T cells. Sci. Transl. Med. 7, 315ra189 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dong, S. et al. The impact of low-dose IL-2 and Treg adoptive cell remedy in sufferers with sort 1 diabetes. JCI Perception 6, e147474 (2021).

  • Marek-Trzonkowska, N. et al. Administration of CD4+CD25highCD127- regulatory T cells preserves β-cell operate in sort 1 diabetes in youngsters. Diabetes Care 35, 1817–1820 (2012).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bender, C. et al. A part 2 randomized trial with autologous polyclonal expanded regulatory T cells in youngsters with new-onset sort 1 diabetes. Sci. Transl. Med. 16, eadn2404 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Uenishi, G. I. et al. GNTI-122: an autologous antigen-specific engineered Treg cell remedy for sort 1 diabetes. JCI Perception 9, e171844 (2024).

  • Venken, Okay., Hellings, N., Liblau, R. & Stinissen, P. Disturbed regulatory T cell homeostasis in a number of sclerosis. Developments Mol. Med. 16, 58–68 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Viglietta, V., Baecher-Allan, C., Weiner, H. L. & Hafler, D. A. Lack of useful suppression by CD4+CD25+ regulatory T cells in sufferers with a number of sclerosis. J. Exp. Med. 199, 971–979 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dominguez-Villar, M. & Hafler, D. A. Regulatory T cells in autoimmune illness. Nat. Immunol. 19, 665–673 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carbone, F. et al. Regulatory T cell proliferative potential is impaired in human autoimmune illness. Nat. Med. 20, 69–74 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Allan, S. E. et al. The function of two FOXP3 isoforms within the era of human CD4+ Tregs. J. Clin. Make investments. 115, 3276–3284 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sumida, T. S. et al. An autoimmune transcriptional circuit drives FOXP3(+) regulatory T cell dysfunction. Sci. Transl. Med. 16, eadp1720 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, X. et al. Immunoswitch nanomodulators allow energetic focusing on and selective proliferation of regulatory T cells for a number of sclerosis remedy. ACS Nano 18, 770–782 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Guo, Q. et al. Engineered PD-1/TIGIT dual-activating cell-membrane nanoparticles with dexamethasone act synergistically to form the effector T cell/Treg steadiness and alleviate systemic lupus erythematosus. Biomaterials 285, 121517 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Saadoun, D. et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N. Engl. J. Med. 365, 2067–2077 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chwojnicki, Okay. et al. Administration of CD4(+)CD25(excessive)CD127(-)FoxP3(+) regulatory T cells for relapsing-remitting a number of sclerosis: a part 1 examine. BioDrugs 35, 47–60 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Katsavos, S. & Coles, A. Alemtuzumab as therapy for a number of sclerosis. Chilly Spring Harb. Perspect. Med. 8, a032029 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gilmore, W. et al. Repopulation of T, B, and NK cells following alemtuzumab therapy in relapsing-remitting a number of sclerosis. J. Neuroinflammation 17, 189 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Freedman, M. S., Kaplan, J. M. & Markovic-Plese, S. Insights into the mechanisms of the therapeutic efficacy of alemtuzumab in a number of sclerosis. J. Clin. Cell. Immunol. 4, 1000152 (2013).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cox, A. L. et al. Lymphocyte homeostasis following therapeutic lymphocyte depletion in a number of sclerosis. Eur. J. Immunol. 35, 3332–3342 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • De Mercanti, S. et al. Alemtuzumab long-term immunologic impact: Treg suppressor operate will increase as much as 24 months. Neurol. Neuroimmunol. Neuroinflamm. 3, e194 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jones, J. L. & Coles, A. J. Mode of motion and scientific research with alemtuzumab. Exp. Neurol. 262 Pt A, 37–43 (2014).

    Article 
    PubMed 

    Google Scholar
     

  • Smolen, J. S., Aletaha, D. & McInnes, I. B. Rheumatoid arthritis. Lancet 388, 2023–2038 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gravallese, E. M. & Firestein, G. S. Rheumatoid arthritis — frequent origins, divergent mechanisms. N. Engl. J. Med. 388, 529–542 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Smith, M. H. & Berman, J. R. What’s rheumatoid arthritis? JAMA 327, 1194 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Ishigaki, Okay. et al. HLA autoimmune danger alleles limit the hypervariable area of T cell receptors. Nat. Genet. 54, 393–402 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bullock, J. et al. Rheumatoid arthritis: a short overview of the therapy. Med. Princ. Pract. 27, 501–507 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ebringer, A. & Rashid, T. Rheumatoid arthritis is attributable to a Proteus urinary tract an infection. APMIS 122, 363–368 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Han, G. M., O’Neil-Andersen, N. J., Zurier, R. B. & Lawrence, D. A. CD4+CD25high T cell numbers are enriched within the peripheral blood of sufferers with rheumatoid arthritis. Cell. Immunol. 253, 92–101 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • van Amelsfort, J. M. et al. CD4(+)CD25(+) regulatory T cells in rheumatoid arthritis: variations within the presence, phenotype, and performance between peripheral blood and synovial fluid. Arthritis Rheum. 50, 2775–2785 (2004).

    Article 
    PubMed 

    Google Scholar
     

  • Liu, M. F. et al. The presence of cytokine-suppressive CD4+CD25+T cells within the peripheral blood and synovial fluid of sufferers with rheumatoid arthritis. Scand. J. Immunol. 62, 312–317 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Möttönen, M. et al. CD4+CD25+T cells with the phenotypic and useful traits of regulatory T cells are enriched within the synovial fluid of sufferers with rheumatoid arthritis. Clin. Exp. Immunol. 140, 360–367 (2005).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lina, C., Conghua, W., Nan, L. & Ping, Z. Mixed therapy of etanercept and MTX reverses Th1/Th2, Th17/Treg imbalance in sufferers with rheumatoid arthritis. J. Clin. Immunol. 31, 596–605 (2011).

    Article 
    PubMed 

    Google Scholar
     

  • Kawashiri, S. Y. et al. CD4+CD25(excessive)CD127(low/-) Treg cell frequency from peripheral blood correlates with illness exercise in sufferers with rheumatoid arthritis. J. Rheumatol. 38, 2517–2521 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kawashiri, S. Y. et al. CD4+CD25 highCD127 low/- Treg cell frequency from peripheral blood correlates with illness exercise in sufferers with rheumatoid arthritis. J. Rheumatol. 38, 2517–2521 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Moradi, B. et al. CD4⁺CD25⁺/highCD127low/⁻ regulatory T cells are enriched in rheumatoid arthritis and osteoarthritis joints-analysis of frequency and phenotype in synovial membrane, synovial fluid and peripheral blood. Arthritis Res. Ther. 16, R97 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cao, D. et al. CD25brightCD4+ regulatory T cells are enriched in infected joints of sufferers with power rheumatic illness. Arthritis Res. Ther. 6, R335–R346 (2004).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jiang, Q. et al. Perform and function of regulatory T cells in rheumatoid arthritis. Entrance. Immunol. 12, 626193 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hashemi, V. et al. Polymorphism of Foxp3 gene impacts the frequency of regulatory T cells and illness exercise in sufferers with rheumatoid arthritis in Iranian inhabitants. Immunol. Lett. 204, 16–22 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Flores-Borja, F., Jury, E. C., Mauri, C. & Ehrenstein, M. R. Defects in CTLA-4 are related to irregular regulatory T cell operate in rheumatoid arthritis. Proc. Natl. Acad. Sci. USA. 105, 19396–19401 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Solar, H. et al. Tim3(+) Foxp3 (+) Treg cells are potent inhibitors of effector T cells and are suppressed in rheumatoid arthritis. Irritation 40, 1342–1350 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Komatsu, N. et al. Pathogenic conversion of Foxp3+ T cells into TH17 cells in autoimmune arthritis. Nat. Med. 20, 62–68 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zaiss, M. M. et al. Treg cells suppress osteoclast formation: a brand new hyperlink between the immune system and bone. Arthritis Rheum. 56, 4104–4112 (2007).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, J. et al. Low-dose IL-2 improved scientific signs by restoring decreased regulatory T cells in sufferers with refractory rheumatoid arthritis: A randomized managed trial. Entrance. Immunol. 13, 947341 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, X. et al. Efficacy and security of low-dose interleukin-2 together with methotrexate in sufferers with energetic rheumatoid arthritis: a randomized, double-blind, placebo-controlled part 2 trial. Sign Transduct. Goal. Ther. 7, 67 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tang, T. T. et al. Atorvastatin upregulates regulatory T cells and reduces scientific illness exercise in sufferers with rheumatoid arthritis. J. Lipid Res. 52, 1023–1032 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, S. X. et al. The efficacy and security of short-term and low-dose IL-2 mixed with tocilizumab to deal with rheumatoid arthritis. Entrance. Immunol. 15, 1359041 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, Y. et al. Downregulation of N6-methyladenosine (m6A) methylation of Sema4D mRNA contributes to Treg dysfunction and allograft rejection. Am. J. Transplant. 25, 930–942 (2025).

  • Steven, P., Perez, V. L. & Sharma, A. Murine fashions of graft versus host illness (GVHD): concentrate on ocular GVHD. Ocul. Surf. 30, 179–186 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Meyer, E. H. et al. Donor regulatory T-cell remedy to forestall graft-versus-host illness. Blood 145, 2012–2024 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zeiser, R. & Blazar, B. R. Acute graft-versus-host illness – biologic course of, prevention, and remedy. N. Engl. J. Med. 377, 2167–2179 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gupta, P. Okay. et al. Decreased Satb1 expression predisposes CD4(+) T standard cells to Treg suppression and promotes transplant survival. Proc. Natl. Acad. Sci. USA. 119, e2205062119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gupta, P. Okay., McIntosh, C. M., Chong, A. S. & Alegre, M. L. The pursuit of transplantation tolerance: new mechanistic insights. Cell. Mol. Immunol. 16, 324–333 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Miller, M. L. et al. Spontaneous restoration of transplantation tolerance after acute rejection. Nat. Commun. 6, 7566 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Han, J. W. et al. Early discount of regulatory T cells is related to acute rejection in liver transplantation beneath tacrolimus-based immunosuppression with basiliximab induction. Am. J. Transplant. 20, 2058–2069 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hu, M. et al. Infiltrating Foxp3(+) regulatory T cells from spontaneously tolerant kidney allografts reveal donor-specific tolerance. Am. J. Transplant. 13, 2819–2830 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Koreth, J. et al. Efficacy, sturdiness, and response predictors of low-dose interleukin-2 remedy for power graft-versus-host illness. Blood 128, 130–137 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bader, C. S. et al. Single-center randomized trial of T-reg graft alone vs T-reg graft plus tacrolimus for the prevention of acute GVHD. Blood Adv. 8, 1105–1115 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Roemhild, A. et al. Regulatory T cells for minimising immune suppression in kidney transplantation: part I/IIa scientific trial. BMJ 371, m3734 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • David, A. F. et al. Mixture cell remedy results in clonal deletion of donor-specific T cells in kidney transplant recipients. EBioMedicine 106, 105239 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sánchez-Fueyo, A. et al. Applicability, security, and organic exercise of regulatory T cell remedy in liver transplantation. Am. J. Transpl. 20, 1125–1136 (2020).

    Article 

    Google Scholar
     

  • Ravichandran, R. et al. Low-dose IL-2 prevents murine power cardiac allograft rejection: Function for IL-2-induced T regulatory cells and exosomes with PD-L1 and CD73. Am. J. Transplant. 22, 2180–2194 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tahvildari, M. et al. In vivo growth of regulatory T cells by low-dose interleukin-2 therapy will increase allograft survival in corneal transplantation. Transplantation 100, 525–532 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Whitehouse, G. et al. IL-2 remedy restores regulatory T-cell dysfunction induced by calcineurin inhibitors. Proc. Natl. Acad. Sci. USA. 114, 7083–7088 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Webster, Okay. E. et al. In vivo growth of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts with out immunosuppression. J. Exp. Med. 206, 751–760 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yamada, Y. et al. Biased IL-2 alerts induce Foxp3-rich pulmonary lymphoid buildings and facilitate long-term lung allograft acceptance in mice. Nat. Commun. 14, 1383 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lim, T. Y. et al. Low dose interleukin-2 selectively expands circulating regulatory T cells however fails to advertise liver allograft tolerance in people. J. Hepatol. 78, 153–164 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Conrad, M. L. et al. Regulatory T cells and their function in allergic illness. Allergy 80, 77–93 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lloyd, C. M. & Hessel, E. M. Features of T cells in bronchial asthma: extra than simply T(H)2 cells. Nat. Rev. Immunol. 10, 838–848 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Harb, H. et al. A regulatory T cell Notch4-GDF15 axis licenses tissue irritation in bronchial asthma. Nat. Immunol. 21, 1359–1370 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aili, A. et al. LPG 18:0 is a basic biomarker of bronchial asthma and inhibits the differentiation and performance of regulatory T-cells. Eur. Respir. J. 64, 2301752 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bates, J. T., Uematsu, S., Akira, S. & Mizel, S. B. Direct stimulation of tlr5+/+ CD11c+ cells is critical for the adjuvant exercise of flagellin. J. Immunol. 182, 7539–7547 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shim, J. U. et al. Flagellin suppresses experimental bronchial asthma by producing regulatory dendritic cells and T cells. J. Allergy Clin. Immunol. 137, 426–435 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, F. et al. A spleen-targeted tolerogenic mRNA-LNPs vaccine for the therapy of experimental bronchial asthma. Adv. Sci. 12, e2412543 (2025).

    Article 

    Google Scholar
     

  • Shirai, T. et al. Celastrol suppresses humoral immune responses and autoimmunity by focusing on the COMMD3/8 advanced. Sci. Immunol. 8, eadc9324 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ndeupen, S. et al. The mRNA-LNP platform’s lipid nanoparticle part utilized in preclinical vaccine research is very inflammatory. iScience 24, 103479 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hibino, S. et al. Inhibition of Nr4a receptors enhances antitumor immunity by breaking Treg-mediated immune tolerance. Most cancers Res. 78, 3027–3040 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tay, C., Tanaka, A. & Sakaguchi, S. Tumor-infiltrating regulatory T cells as targets of most cancers immunotherapy. Most cancers Cell 41, 450–465 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Arce Vargas, F. et al. Fc-optimized anti-CD25 depletes tumor-infiltrating regulatory T cells and synergizes with PD-1 blockade to eradicate established tumors. Immunity 46, 577–586 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ge, Z., Peppelenbosch, M. P., Sprengers, D. & Kwekkeboom, J. TIGIT, the following step in the direction of profitable mixture immune checkpoint remedy in most cancers. Entrance. Immunol. 12, 699895 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sugiyama, D. et al. Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in people. Proc. Natl. Acad. Sci. USA. 110, 17945–17950 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kidani, Y. et al. CCR8-targeted particular depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting reminiscence. Proc. Natl. Acad. Sci. USA. 119, e2114282119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Eschweiler, S. et al. Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs. Nature 605, 741–746 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, Y. et al. Regulatory T-cell depletion alters the tumor microenvironment and accelerates pancreatic carcinogenesis. Most cancers Discov. 10, 422–439 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Becker, M. et al. Area of interest-specific management of tissue operate by regulatory T cells-Present challenges and views for focusing on metabolic illness. Cell Metab. 36, 229–239 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhao, X. Y. et al. The obesity-induced adipokine sST2 exacerbates adipose T(reg) and ILC2 depletion and promotes insulin resistance. Sci. Adv. 6, eaay6191 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gilleron, J. et al. Rab4b deficiency in T cells promotes adipose Treg/Th17 imbalance, adipose tissue dysfunction, and insulin resistance. Cell Rep. 25, 3329–3341.e3325 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, G. et al. Adipose-tissue Treg cells restrain differentiation of stromal adipocyte precursors to advertise insulin sensitivity and metabolic homeostasis. Immunity 57, 1345–1359.e1345 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schmidleithner, L. et al. Enzymatic exercise of HPGD in Treg cells suppresses Tconv cells to take care of adipose tissue homeostasis and forestall metabolic dysfunction. Immunity 50, 1232–1248.e1214 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wernstedt Asterholm, I. et al. Adipocyte irritation is crucial for wholesome adipose tissue growth and reworking. Cell Metab. 20, 103–118 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nayer, B. et al. Native administration of regulatory T cells promotes tissue therapeutic. Nat. Commun. 15, 7863 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fujisaki, J. et al. In vivo imaging of Treg cells offering immune privilege to the haematopoietic stem-cell area of interest. Nature 474, 216–219 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, J., Tan, J., Martino, M. M. & Lui, Okay. O. Regulatory T-cells: potential regulator of tissue restore and regeneration. Entrance. Immunol. 9, 585 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Loffredo, L. F., Savage, T. M., Ringham, O. R. & Arpaia, N. Treg-tissue cell interactions in restore and regeneration. J. Exp. Med. 221, e20231244 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Delacher, M. et al. Single-cell chromatin accessibility panorama identifies tissue restore program in human regulatory T cells. Immunity 54, 702–720.e717 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Delacher, M. et al. Precursors for nonlymphoid-tissue Treg cells reside in secondary lymphoid organs and are programmed by the transcription issue BATF. Immunity 52, 295–312.e211 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Delacher, M. et al. Rbpj expression in regulatory T cells is crucial for restraining T(H)2 responses. Nat. Commun. 10, 1621 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Delacher, M. et al. Genome-wide DNA-methylation panorama defines specialization of regulatory T cells in tissues. Nat. Immunol. 18, 1160–1172 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vasanthakumar, A. et al. The transcriptional regulators IRF4, BATF and IL-33 orchestrate improvement and upkeep of adipose tissue-resident regulatory T cells. Nat. Immunol. 16, 276–285 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schiering, C. et al. The alarmin IL-33 promotes regulatory T-cell operate within the gut. Nature 513, 564–568 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, R. et al. Progranulin-dependent restore operate of regulatory T cells drives bone-fracture therapeutic. J. Clin. Make investments. 135, e180679 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, M. & Zhang, S. T cells in fibrosis and fibrotic ailments. Entrance. Immunol. 11, 1142 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tang, T. T. et al. Regulatory T cells ameliorate cardiac reworking after myocardial infarction. Primary Res. Cardiol. 107, 232 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Alshoubaki, Y. Okay. et al. Tregs delivered post-myocardial infarction undertake an injury-specific phenotype selling cardiac restore by way of macrophages in mice. Nat. Commun. 15, 6480 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kvakan, H. et al. Regulatory T cells ameliorate angiotensin II-induced cardiac injury. Circulation 119, 2904–2912 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bansal, S. S. et al. Dysfunctional and proinflammatory regulatory T-lymphocytes are important for adversarial cardiac reworking in ischemic cardiomyopathy. Circulation 139, 206–221 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lo Re, S. et al. Platelet-derived progress factor-producing CD4+ Foxp3+ regulatory T lymphocytes promote lung fibrosis. Am. J. Respir. Crit. Care Med. 184, 1270–1281 (2011).

    Article 
    PubMed 

    Google Scholar
     

  • Chen, J. et al. Glycyrrhetinic acid mitigates radiation-induced pulmonary fibrosis by way of inhibiting the secretion of TGF-β1 by Treg cells. Int. J. Radiat. Oncol. Biol. Phys. 118, 218–230 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Xiong, S. et al. Treg depletion attenuates irradiation-induced pulmonary fibrosis by decreasing fibrocyte accumulation, inducing Th17 response, and shifting IFN-γ, IL-12/IL-4, IL-5 steadiness. Immunobiology 220, 1284–1291 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yan, S. et al. Low expression of lipoic acid synthase aggravates silica-induced pulmonary fibrosis by inhibiting the differentiation of Tregs in mice. Antioxid. Redox Sign 41, 216–232 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liu, T. et al. Baicalin alleviates silica-induced lung irritation and fibrosis by inhibiting the Th17 response in C57BL/6 mice. J. Nat. Prod. 78, 3049–3057 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Frantz, C. et al. Driving function of interleukin-2-related regulatory CD4+T cell deficiency within the improvement of lung fibrosis and vascular reworking in a mouse mannequin of systemic sclerosis. Arthritis Rheumatol. 74, 1387–1398 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ikeno, Y. et al. Foxp3+ regulatory T cells inhibit CCl(4)-induced liver irritation and fibrosis by regulating tissue mobile immunity. Entrance. Immunol. 11, 584048 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Savage, T. M. et al. Amphiregulin from regulatory T cells promotes liver fibrosis and insulin resistance in non-alcoholic steatohepatitis. Immunity 57, 303–318.e306 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Walker, M. D. & Shane, E. Postmenopausal osteoporosis. N. Engl. J. Med. 389, 1979–1991 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Bonnet, N. et al. RANKL inhibition improves muscle energy and insulin sensitivity and restores bone mass. J. Clin. Make investments. 129, 3214–3223 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fischer, L. et al. Foxp3(+) Regulatory T Cells in Bone and Hematopoietic Homeostasis. Entrance. Endocrinol. 10, 578 (2019).

    Article 

    Google Scholar
     

  • Shieh, A., Epeldegui, M., Karlamangla, A. S. & Greendale, G. A. Intestine permeability, irritation, and bone density throughout the menopause transition. JCI Perception 5, e134092 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, X. et al. T cell-depleting nanoparticles ameliorate bone loss by decreasing activated T cells and regulating the Treg/Th17 steadiness. Bioact. Mater. 6, 3150–3163 (2021).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Luo, C. Y., Wang, L., Solar, C. & Li, D. J. Estrogen enhances the features of CD4(+)CD25(+)Foxp3(+) regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro. Cell. Mol. Immunol. 8, 50–58 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Guo, M. et al. Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg steadiness and intestine microbiota construction. Intestine Microbes 15, 2190304 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dar, H. Y. et al. Lactobacillus acidophilus inhibits bone loss and will increase bone heterogeneity in osteoporotic mice by way of modulating Treg-Th17 cell steadiness. Bone Rep. 8, 46–56 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hartemann, A. et al. Low-dose interleukin 2 in sufferers with sort 1 diabetes: a part 1/2 randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 1, 295–305 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • He, J. et al. Efficacy and security of low-dose IL-2 within the therapy of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial. Ann. Rheum. Dis. 79, 141–149 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Saxena, V., Lakhan, R., Iyyathurai, J. & Bromberg, J. S. Mechanisms of exTreg induction. Eur. J. Immunol. 51, 1956–1967 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lal, G. et al. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J. Immunol. 182, 259–273 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Skartsis, N. et al. IL-6 and TNFα drive in depth proliferation of human Tregs with out compromising their lineage stability or operate. Entrance. Immunol. 12, 783282 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saigusa, R. et al. Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human heart problems. Nat. Cardiovasc. Res. 1, 462–475 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jiang, Z. et al. TMED4 facilitates regulatory T cell suppressive operate by way of ROS homeostasis in tumor and autoimmune mouse fashions. J. Clin. Make investments. 135, e179874 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, Y. et al. The E3 ligase Hrd1 stabilizes Tregs by antagonizing inflammatory cytokine-induced ER stress response. JCI Perception 4, e121887 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Freuchet, A. et al. Identification of human exT(reg) cells as CD16(+)CD56(+) cytotoxic CD4(+) T cells. Nat. Immunol. 24, 1748–1761 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Alissafi, T. et al. Mitochondrial oxidative injury underlies regulatory T cell defects in autoimmunity. Cell Metab. 32, 591–604.e597 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Parashar, S. et al. ER stress induced mitochondrial dysfunction drives Treg instability in coronary artery illness. EMBO Mol. Med. 17, 3250–3274 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arvey, A. et al. Genetic and epigenetic variation within the lineage specification of regulatory T cells. eLife 4, e07571 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yadav, M. et al. Neuropilin-1 distinguishes pure and inducible regulatory T cells amongst regulatory T cell subsets in vivo. J. Exp. Med. 209, 1713–1722, s1711–1719 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weiss, J. M. et al. Neuropilin 1 is expressed on thymus-derived pure regulatory T cells, however not mucosa-generated induced Foxp3+ T reg cells. J. Exp. Med. 209, 1723–1742, s1721 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Thornton, A. M. et al. Expression of Helios, an Ikaros transcription issue member of the family, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184, 3433–3441 (2010).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Elkord, E. Helios shouldn’t be cited as a marker of human thymus-derived Tregs. Commentary: helios(+) and helios(-) cells coexist throughout the pure FOXP3(+) T regulatory cell subset in people. Entrance. Immunol. 7, 276 (2016).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ziegler, S. F. FOXP3: of mice and males. Annu. Rev. Immunol. 24, 209–226 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Du, J. et al. FOXP3 exon 2 controls T(reg) stability and autoimmunity. Sci. Immunol. 7, eabo5407 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Miyara, M. & Sakaguchi, S. Human FoxP3(+)CD4(+) regulatory T cells: their knowns and unknowns. Immunol. Cell Biol. 89, 346–351 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Balcerek, J. et al. Polyclonal regulatory T cell manufacturing beneath cGMP: a decade of expertise. Entrance. Immunol. 12, 744763 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Brunstein, C. G. et al. Umbilical twine blood-derived T regulatory cells to forestall GVHD: kinetics, toxicity profile, and scientific impact. Blood 127, 1044–1051 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Obradovic, A. et al. Systematic elucidation and pharmacological focusing on of tumor-infiltrating regulatory T cell grasp regulators. Most cancers Cell 41, 933–949.e911 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ramirez, R. N. et al. FoxP3 associates with enhancer-promoter loops to control T(reg)-specific gene expression. Sci. Immunol. 7, eabj9836 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, R. et al. Plant exosomes fused with engineered mesenchymal stem cell-derived nanovesicles for synergistic remedy of autoimmune pores and skin problems. J. Extracell. Vesicles 12, e12361 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McHugh, M. D. et al. Paracrine co-delivery of TGF-β and IL-2 utilizing CD4-targeted nanoparticles for induction and upkeep of regulatory T cells. Biomaterials 59, 172–181 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Haist, M., Mailänder, V. & Bros, M. Nanodrugs focusing on T cells in tumor remedy. Entrance. Immunol. 13, 912594 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ramanan, D. et al. Homeostatic, repertoire and transcriptional relationships between colon T regulatory cell subsets. Proc. Natl. Acad. Sci. USA. 120, e2311566120 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dixon, M. L. et al. Reworking of the tumor microenvironment by way of disrupting Blimp1(+) effector Treg exercise augments response to anti-PD-1 blockade. Mol. Most cancers 20, 150 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Muñoz-Rojas, A. R. & Mathis, D. Tissue regulatory T cells: regulatory chameleons. Nat. Rev. Immunol. 21, 597–611 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kalekar, L. A. et al. Regulatory T cells in pores and skin are uniquely poised to suppress profibrotic immune responses. Sci. Immunol. 4, eaaw2910 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Malhotra, N. et al. RORα-expressing T regulatory cells restrain allergic pores and skin irritation. Sci. Immunol. 3, eaao6923 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Min, H. Okay. et al. Protein inhibitor of activated STAT3 reduces peripheral arthritis and intestine irritation and regulates the Th17/Treg cell imbalance by way of STAT3 signaling in a mouse mannequin of spondyloarthritis. J. Transl. Med. 17, 18 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Asakawa, M. et al. A novel JAK-STAT inhibitor, 2-[(3-Carbamoyl-2-thienyl)amino]-2-oxoethyl(2,6-dichlorophenyl)acetate, suppresses helper T cell differentiation in vitro and collagen-induced arthritis in vivo. Biochem. Biophys. Res. Commun. 468, 766–773 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Strainic, M. G. et al. Absence of signaling into CD4⁺ cells by way of C3aR and C5aR permits autoinductive TGF-β1 signaling and induction of Foxp3⁺ regulatory T cells. Nat. Immunol. 14, 162–171 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lim, S. M. et al. Neomangiferin modulates the Th17/Treg steadiness and ameliorates colitis in mice. Phytomedicine 23, 131–140 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shen, Y. et al. Sorafenib promotes Treg cell differentiation to compromise its efficacy by way of VEGFR/AKT/Foxo1 signaling in hepatocellular carcinoma. Cell. Mol. Gastroenterol. Hepatol. 19, 101454 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hui, W. et al. Ginkgo biloba extract promotes Treg differentiation to ameliorate ischemic stroke by way of inhibition of HIF-1α/HK2 pathway. Phytother. Res. 37, 5821–5836 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lv, Q. et al. Norisoboldine, a pure AhR agonist, promotes Treg differentiation and attenuates colitis by way of focusing on glycolysis and subsequent NAD(+)/SIRT1/SUV39H1/H3K9me3 signaling pathway. Cell Loss of life Dis. 9, 258 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Procaccini, C. et al. Alerts of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant within the management of Treg cell proliferative potential. Immunity 54, 1543–1560.e1546 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Court docket, A. C. et al. Mitochondrial switch from MSCs to T cells induces Treg differentiation and restricts inflammatory response. EMBO Rep. 21, e48052 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ramos, G. P. et al. G9a modulates lipid metabolism in CD4 T cells to control intestinal irritation. Gastroenterology 164, 256–271.e210 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Luo, X. et al. Innovative: TGF-beta-induced expression of Foxp3 in T cells is mediated via inactivation of ERK. J. Immunol. 180, 2757–2761 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, J. et al. Melatonin, an endogenous hormone, modulates Th17 cells by way of the reactive-oxygen species/TXNIP/HIF-1α axis to alleviate autoimmune uveitis. J. Neuroinflammation 19, 124 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Daenthanasanmak, A. et al. Focusing on Sirt-1 controls GVHD by inhibiting T-cell allo-response and selling Treg stability in mice. Blood 133, 266–279 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Akamatsu, M. et al. Conversion of antigen-specific effector/reminiscence T cells into Foxp3-expressing T(reg) cells by inhibition of CDK8/19. Sci. Immunol. 4, eaaw2707 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Dinesh, P. & Rasool, M. Berberine mitigates IL-21/IL-21R mediated autophagic inflow in fibroblast-like synoviocytes and regulates Th17/Treg imbalance in rheumatoid arthritis. Apoptosis 24, 644–661 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Arai, M. et al. Oral antigen publicity beneath costimulation blockade induces Treg cells to ascertain immune tolerance. J. Exp. Med. 223, e20251635 (2026).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhou, H. et al. A peptide encoded by pri-miRNA-31 represses autoimmunity by selling T(reg) differentiation. EMBO Rep. 23, e53475 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Huang, Q. et al. Bioactive compounds from ShenFuShanYuRou decoction improve Treg cell operate towards hemorrhagic shock damage by way of Stat1- and Gbp5-dependent FOXP3 induction. Clin. Transl. Med. 14, e70047 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sawitzki, B. et al. Regulatory cell remedy in kidney transplantation (The ONE Examine): a harmonised design and evaluation of seven non-randomised, single-arm, part 1/2 A trials. Lancet 395, 1627–1639 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gauthier, J. M. et al. The rising function of regulatory T cells following lung transplantation. Immunol. Rev. 292, 194–208 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhao, Y. et al. ADAR1 improved Treg cell operate via the miR-21b/Foxp3 axis and inhibits the development of acute graft-versus-host illness after allogeneic hematopoietic stem cell transplantation. Int. Immunopharmacol. 115, 109620 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Michalek, R. D. et al. Innovative: distinct glycolytic and lipid oxidative metabolic packages are important for effector and regulatory CD4+T cell subsets. J. Immunol. 186, 3299–3303 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Berod, L. et al. De novo fatty acid synthesis controls the destiny between regulatory T and T helper 17 cells. Nat. Med. 20, 1327–1333 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gerriets, V. A. et al. Foxp3 and Toll-like receptor signaling steadiness T(reg) cell anabolic metabolism for suppression. Nat. Immunol. 17, 1459–1466 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, L. et al. TLR8-mediated metabolic management of human treg operate: a mechanistic goal for most cancers immunotherapy. Cell Metab. 29, 103–123.e105 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rokade, S., Damani, A. M., Oft, M. & Emmerich, J. IL-2 based mostly most cancers immunotherapies: an evolving paradigm. Entrance. Immunol. 15, 1433989 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Friedmann, M. C., Migone, T. S., Russell, S. M. & Leonard, W. J. Completely different interleukin 2 receptor beta-chain tyrosines couple to no less than two signaling pathways and synergistically mediate interleukin 2-induced proliferation. Proc. Natl. Acad. Sci. USA. 93, 2077–2082 (1996).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

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