{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:53:25Z","timestamp":1788900805370,"version":"build-2803163510"},"publisher-location":"Singapore","reference-count":159,"publisher":"Springer Nature Singapore","isbn-type":[{"value":"9789819997800","type":"print"},{"value":"9789819997817","type":"electronic"}],"license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024]]},"DOI":"10.1007\/978-981-99-9781-7_5","type":"book-chapter","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T06:07:51Z","timestamp":1710223671000},"page":"67-82","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Regulatory T Cells for Control of Autoimmunity"],"prefix":"10.1007","author":[{"given":"Ryoji","family":"Kawakami","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"5_CR1","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1111\/imr.12398","volume":"271","author":"N Kurd","year":"2016","unstructured":"Kurd N, Robey EA. T-cell selection in the thymus: a spatial and temporal perspective. Immunol Rev. 2016;271:114\u201326.","journal-title":"Immunol Rev"},{"key":"5_CR2","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1146\/annurev-immunol-100219-020937","volume":"38","author":"PA Savage","year":"2020","unstructured":"Savage PA, Klawon DEJ, Miller CH. Regulatory T cell development. Annu Rev Immunol. 2020;38:421\u201353.","journal-title":"Annu Rev Immunol"},{"key":"5_CR3","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.it.2017.07.010","volume":"38","author":"H Takaba","year":"2017","unstructured":"Takaba H, Takayanagi H. The mechanisms of T cell selection in the thymus. Trends Immunol. 2017;38:805\u201316.","journal-title":"Trends Immunol"},{"key":"5_CR4","doi-asserted-by":"crossref","unstructured":"Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol. 1995;155(3):1151\u201364.","DOI":"10.4049\/jimmunol.155.3.1151"},{"key":"5_CR5","doi-asserted-by":"crossref","unstructured":"Asano M, Toda M, Sakaguchi N, Sakaguchi S. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med. 1996;184(2):387\u201396.","DOI":"10.1084\/jem.184.2.387"},{"key":"5_CR6","doi-asserted-by":"crossref","unstructured":"Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otsuka F, et al. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol. 1999;158(10):4642\u201353.","DOI":"10.4049\/jimmunol.162.9.5317"},{"key":"5_CR7","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/83713","volume":"27","author":"CL Bennett","year":"2001","unstructured":"Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001;27:20\u20131.","journal-title":"Nat Genet"},{"key":"5_CR8","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/83707","volume":"27","author":"RS Wildin","year":"2001","unstructured":"Wildin RS, Ramsdell F, Peake J, et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet. 2001;27:18\u201320.","journal-title":"Nat Genet"},{"key":"5_CR9","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.1016\/S0140-6736(23)00457-9","volume":"401","author":"N Conrad","year":"2023","unstructured":"Conrad N, Misra S, Verbakel JY, et al. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK. Lancet. 2023;401:1878\u201390.","journal-title":"Lancet"},{"key":"5_CR10","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1016\/j.jaci.2018.10.026","volume":"142","author":"A-M Cepika","year":"2018","unstructured":"Cepika A-M, Sato Y, Liu JM-H, et al. Tregopathies: monogenic diseases resulting in regulatory T-cell deficiency. J Allergy Clin Immunol. 2018;142:1679\u201395.","journal-title":"J Allergy Clin Immunol"},{"key":"5_CR11","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.immuni.2020.04.006","volume":"52","author":"N Ohkura","year":"2020","unstructured":"Ohkura N, Yasumizu Y, Kitagawa Y, et al. Regulatory T cell-specific epigenomic region variants are a key determinant of susceptibility to common autoimmune diseases. Immunity. 2020;52:1119\u20131132.e4.","journal-title":"Immunity"},{"key":"5_CR12","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/s41588-022-01066-3","volume":"54","author":"B Soskic","year":"2022","unstructured":"Soskic B, Cano-Gamez E, Smyth DJ, et al. Immune disease risk variants regulate gene expression dynamics during CD4+ T cell activation. Nat Genet. 2022;54:817\u201326.","journal-title":"Nat Genet"},{"key":"5_CR13","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1126\/science.1160062","volume":"322","author":"K Wing","year":"2008","unstructured":"Wing K, Onishi Y, Prieto-Martin P, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322:271\u20135.","journal-title":"Science"},{"key":"5_CR14","doi-asserted-by":"publisher","first-page":"E2116","DOI":"10.1073\/pnas.1307185110","volume":"110","author":"T Yamaguchi","year":"2013","unstructured":"Yamaguchi T, Kishi A, Osaki M, et al. Construction of self-recognizing regulatory T cells from conventional T cells by controlling CTLA-4 and IL-2 expression. Proc Natl Acad Sci U S A. 2013;110:E2116\u201325.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5_CR15","doi-asserted-by":"publisher","first-page":"10113","DOI":"10.1073\/pnas.0711106105","volume":"105","author":"Y Onishi","year":"2008","unstructured":"Onishi Y, Fehervari Z, Yamaguchi T, Sakaguchi S. Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc Natl Acad Sci U S A. 2008;105:10113\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5_CR16","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1038\/s41590-022-01289-w","volume":"23","author":"A Kennedy","year":"2022","unstructured":"Kennedy A, Waters E, Rowshanravan B, et al. Differences in CD80 and CD86 transendocytosis reveal CD86 as a key target for CTLA-4 immune regulation. Nat Immunol. 2022;23:1365\u201378.","journal-title":"Nat Immunol"},{"key":"5_CR17","doi-asserted-by":"publisher","first-page":"eaaw0902","DOI":"10.1126\/sciimmunol.aaw0902","volume":"4","author":"V Ovcinnikovs","year":"2019","unstructured":"Ovcinnikovs V, Ross EM, Petersone L, et al. CTLA-4-mediated transendocytosis of costimulatory molecules primarily targets migratory dendritic cells. Sci Immunol. 2019;4:eaaw0902. https:\/\/doi.org\/10.1126\/sciimmunol.aaw0902.","journal-title":"Sci Immunol"},{"key":"5_CR18","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1126\/science.1202947","volume":"332","author":"OS Qureshi","year":"2011","unstructured":"Qureshi OS, Zheng Y, Nakamura K, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science. 2011;332:600\u20133.","journal-title":"Science"},{"key":"5_CR19","doi-asserted-by":"publisher","first-page":"e2023739118","DOI":"10.1073\/pnas.2023739118","volume":"118","author":"M Tekguc","year":"2021","unstructured":"Tekguc M, Wing JB, Osaki M, et al. Treg-expressed CTLA-4 depletes CD80\/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells. Proc Natl Acad Sci U S A. 2021;118:e2023739118. https:\/\/doi.org\/10.1073\/pnas.2023739118.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5_CR20","doi-asserted-by":"crossref","unstructured":"Osaki M, Sakaguchi S. Soluble CTLA-4 mainly produced by Treg cells inhibits type 1 inflammation without hindering type 2 immunity to allow for inflammation resolution. bioRxiv. 2023. p. 2023.05.26.542386. https:\/\/www.biorxiv.org\/content\/10.1101\/2023.05.26.542386v2.abstract.","DOI":"10.1101\/2023.05.26.542386"},{"key":"5_CR21","doi-asserted-by":"crossref","unstructured":"Maeda Y, Nishikawa H, Sugiyama D, et al. Detection of self-reactive CD8+ T cells with an anergic phenotype in healthy individuals. Science. 2014;346:1536\u201340.","DOI":"10.1126\/science.aaa1292"},{"key":"5_CR22","doi-asserted-by":"publisher","first-page":"eaat1482","DOI":"10.1126\/sciimmunol.aat1482","volume":"3","author":"AK Abbas","year":"2018","unstructured":"Abbas AK, Trotta E, Simeonov DR, et al. Revisiting IL-2: biology and therapeutic prospects. Sci Immunol. 2018;3:eaat1482. https:\/\/doi.org\/10.1126\/sciimmunol.aat1482.","journal-title":"Sci Immunol"},{"key":"5_CR23","doi-asserted-by":"publisher","first-page":"e20212391","DOI":"10.1084\/JEM.20212391","volume":"219","author":"CE Whyte","year":"2022","unstructured":"Whyte CE, Singh K, Burton OT, et al. Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits. J Exp Med. 2022;219:e20212391. https:\/\/doi.org\/10.1084\/JEM.20212391.","journal-title":"J Exp Med"},{"key":"5_CR24","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1038\/ni1536","volume":"8","author":"P Pandiyan","year":"2007","unstructured":"Pandiyan P, Zheng L, Ishihara S, et al. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol. 2007;8:1353\u201362.","journal-title":"Nat Immunol"},{"key":"5_CR25","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.4049\/jimmunol.178.3.1251","volume":"178","author":"R Sharma","year":"2007","unstructured":"Sharma R, Zheng L, Deshmukh US, et al. A regulatory T cell-dependent novel function of CD25 (IL-2Ralpha) controlling memory CD8(+) T cell homeostasis. J Immunol. 2007;178:1251\u20135.","journal-title":"J Immunol"},{"key":"5_CR26","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/j.celrep.2018.10.002","volume":"25","author":"MY Fan","year":"2018","unstructured":"Fan MY, Low JS, Tanimine N, et al. Differential roles of IL-2 signaling in developing versus mature Tregs. Cell Rep. 2018;25:1204\u20131213.e4.","journal-title":"Cell Rep"},{"key":"5_CR27","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1146\/annurev.immunol.26.021607.090357","volume":"26","author":"TR Malek","year":"2008","unstructured":"Malek TR. The biology of interleukin-2. Annu Rev Immunol. 2008;26:453\u201379.","journal-title":"Annu Rev Immunol"},{"key":"5_CR28","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1084\/jem.20041982","volume":"201","author":"R Setoguchi","year":"2005","unstructured":"Setoguchi R, Hori S, Takahashi T, Sakaguchi S. Homeostatic maintenance of natural Foxp3+ CD25+ CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med. 2005;201:723\u201335.","journal-title":"J Exp Med"},{"key":"5_CR29","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1084\/jem.190.7.995","volume":"190","author":"C Asseman","year":"1999","unstructured":"Asseman C, Mauze S, Leach MW, et al. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med. 1999;190:995\u20131004.","journal-title":"J Exp Med"},{"key":"5_CR30","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.immuni.2008.02.017","volume":"28","author":"YP Rubtsov","year":"2008","unstructured":"Rubtsov YP, Rasmussen JP, Chi EY, et al. Regulatory T cell-derived Interleukin-10 limits inflammation at environmental interfaces. Immunity. 2008;28:546\u201358.","journal-title":"Immunity"},{"key":"5_CR31","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1084\/jem.20080308","volume":"205","author":"J Andersson","year":"2008","unstructured":"Andersson J, Tran DQ, Pesu M, et al. CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-\u03b2-dependent manner. J Exp Med. 2008;205:1975\u201381.","journal-title":"J Exp Med"},{"key":"5_CR32","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1084\/jem.194.5.629","volume":"194","author":"K Nakamura","year":"2001","unstructured":"Nakamura K, Kitani A, Strober W. Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med. 2001;194:629\u201344.","journal-title":"J Exp Med"},{"key":"5_CR33","doi-asserted-by":"publisher","first-page":"13445","DOI":"10.1073\/pnas.0901944106","volume":"106","author":"DQ Tran","year":"2009","unstructured":"Tran DQ, Andersson J, Wang R, et al. GARP (LRRC32) is essential for the surface expression of latent TGF-\u03b2 on platelets and activated FOXP3+ regulatory T cells. Proc Natl Acad Sci. 2009;106:13445\u201350.","journal-title":"Proc Natl Acad Sci"},{"key":"5_CR34","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/j.immuni.2015.04.012","volume":"42","author":"JJ Worthington","year":"2015","unstructured":"Worthington JJ, Kelly A, Smedley C, et al. Integrin \u03b1v\u03b28-mediated TGF-\u03b2 activation by effector regulatory T cells is essential for suppression of T-cell-mediated inflammation. Immunity. 2015;42:903\u201315.","journal-title":"Immunity"},{"key":"5_CR35","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1084\/jem.20062512","volume":"204","author":"S Deaglio","year":"2007","unstructured":"Deaglio S, Dwyer KM, Gao W, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204:1257\u201365.","journal-title":"J Exp Med"},{"key":"5_CR36","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1002\/eji.201141578","volume":"42","author":"J Bodor","year":"2012","unstructured":"Bodor J, Bopp T, Vaeth M, et al. Cyclic AMP underpins suppression by regulatory T cells. Eur J Immunol. 2012;42:1375\u201384.","journal-title":"Eur J Immunol"},{"key":"5_CR37","doi-asserted-by":"publisher","first-page":"4017","DOI":"10.4049\/jimmunol.0803310","volume":"182","author":"T Bopp","year":"2009","unstructured":"Bopp T, Dehzad N, Reuter S, et al. Inhibition of cAMP degradation improves regulatory T cell-mediated suppression. J Immunol. 2009;182:4017\u201324.","journal-title":"J Immunol"},{"key":"5_CR38","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3389\/fimmu.2016.00315","volume":"7","author":"M Klein","year":"2016","unstructured":"Klein M, Bopp T. Cyclic AMP represents a crucial component of Treg cell-mediated immune regulation. Front Immunol. 2016;7:315.","journal-title":"Front Immunol"},{"key":"5_CR39","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1016\/j.cell.2013.10.054","volume":"155","author":"D Burzyn","year":"2013","unstructured":"Burzyn D, Kuswanto W, Kolodin D, et al. A special population of regulatory T cells potentiates muscle repair. Cell. 2013;155:1282\u201395.","journal-title":"Cell"},{"key":"5_CR40","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/nature06306","volume":"450","author":"LW Collison","year":"2007","unstructured":"Collison LW, Workman CJ, Kuo TT, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 2007;450:566\u20139.","journal-title":"Nature"},{"key":"5_CR41","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41577-021-00519-w","volume":"21","author":"AR Mu\u00f1oz-Rojas","year":"2021","unstructured":"Mu\u00f1oz-Rojas AR, Mathis D. Tissue regulatory T cells: regulatory chameleons. Nat Rev Immunol. 2021;21:597\u2013611.","journal-title":"Nat Rev Immunol"},{"key":"5_CR42","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1038\/nm.2002","volume":"15","author":"M Feuerer","year":"2009","unstructured":"Feuerer M, Herrero L, Cipolletta D, et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med. 2009;15:930\u20139.","journal-title":"Nat Med"},{"key":"5_CR43","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/s41586-018-0824-5","volume":"565","author":"M Ito","year":"2019","unstructured":"Ito M, Komai K, Mise-Omata S, et al. Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery. Nature. 2019;565:246\u201350.","journal-title":"Nature"},{"key":"5_CR44","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/j.immuni.2012.05.031","volume":"37","author":"MA Koch","year":"2012","unstructured":"Koch MA, Thomas KR, Perdue NR, et al. T-bet(+) Treg cells undergo abortive Th1 cell differentiation due to impaired expression of IL-12 receptor \u03b22. Immunity. 2012;37:501\u201310.","journal-title":"Immunity"},{"key":"5_CR45","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/ni.1731","volume":"10","author":"MA Koch","year":"2009","unstructured":"Koch MA, Tucker-Heard G, Perdue NR, et al. The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat Immunol. 2009;10:595\u2013602.","journal-title":"Nat Immunol"},{"key":"5_CR46","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/nature22360","volume":"546","author":"AG Levine","year":"2017","unstructured":"Levine AG, Medoza A, Hemmers S, et al. Stability and function of regulatory T cells expressing the transcription factor T-bet. Nature. 2017;546:421. https:\/\/doi.org\/10.1038\/nature22360.","journal-title":"Nature"},{"key":"5_CR47","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1016\/j.immuni.2023.06.003","volume":"56","author":"MA Moreno Ayala","year":"2023","unstructured":"Moreno Ayala MA, Campbell TF, Zhang C, et al. CXCR3 expression in regulatory T cells drives interactions with type I dendritic cells in tumors to restrict CD8+ T cell antitumor immunity. Immunity. 2023;56:1613\u20131630.e5.","journal-title":"Immunity"},{"key":"5_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112813","volume":"42","author":"M Okamoto","year":"2023","unstructured":"Okamoto M, Sasai M, Kuratani A, et al. A genetic method specifically delineates Th1-type Treg cells and their roles in tumor immunity. Cell Rep. 2023;42:112813.","journal-title":"Cell Rep"},{"key":"5_CR49","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/nm.2426","volume":"17","author":"Y Chung","year":"2011","unstructured":"Chung Y, Tanaka S, Chu F, et al. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat Med. 2011;17:983\u20138.","journal-title":"Nat Med"},{"key":"5_CR50","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1038\/nm.2425","volume":"17","author":"MA Linterman","year":"2011","unstructured":"Linterman MA, Pierson W, Lee SK, et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med. 2011;17:975\u201382.","journal-title":"Nat Med"},{"key":"5_CR51","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1126\/science.aac4263","volume":"349","author":"C Ohnmacht","year":"2015","unstructured":"Ohnmacht C, Park JH, Cording S, et al. The microbiota regulates type 2 immunity through ROR\u03b3t+ T cells. Science. 2015;349:989. https:\/\/doi.org\/10.1126\/science.aac4263.","journal-title":"Science"},{"key":"5_CR52","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1126\/science.aaa9420","volume":"349","author":"E Sefik","year":"2015","unstructured":"Sefik E, Geva-Zatorsky N, Oh S, et al. Individual intestinal symbionts induce a distinct population of ROR\u03b3 + regulatory T cells. Science. 2015;349:993. https:\/\/doi.org\/10.1126\/science.aaa9420.","journal-title":"Science"},{"key":"5_CR53","doi-asserted-by":"publisher","first-page":"4503","DOI":"10.1172\/JCI57456","volume":"121","author":"EA Wohlfert","year":"2011","unstructured":"Wohlfert EA, Grainger JR, Bouladoux N, et al. GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice. J Clin Invest. 2011;121:4503\u201315.","journal-title":"J Clin Invest"},{"key":"5_CR54","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/nri.2016.26","volume":"16","author":"MO Li","year":"2016","unstructured":"Li MO, Rudensky AY. T cell receptor signalling in the control of regulatory T cell differentiation and function. Nat Rev Immunol. 2016;16:220\u201333.","journal-title":"Nat Rev Immunol"},{"key":"5_CR55","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1038\/ni.3466","volume":"17","author":"R Newton","year":"2016","unstructured":"Newton R, Priyadharshini B, Turka LA. Immunometabolism of regulatory T cells. Nat Immunol. 2016;17:618\u201325.","journal-title":"Nat Immunol"},{"key":"5_CR56","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1146\/annurev-immunol-020711-075024","volume":"30","author":"JD Powell","year":"2012","unstructured":"Powell JD, Pollizzi KN, Heikamp EB, Horton MR. Regulation of immune responses by mTOR. Annu Rev Immunol. 2012;30:39\u201368.","journal-title":"Annu Rev Immunol"},{"key":"5_CR57","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nature12428","volume":"501","author":"GM Delgoffe","year":"2013","unstructured":"Delgoffe GM, Woo S-R, Turnis ME, et al. Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature. 2013;501:252\u20136.","journal-title":"Nature"},{"key":"5_CR58","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/ni.3077","volume":"16","author":"A Huynh","year":"2015","unstructured":"Huynh A, DuPage M, Priyadharshini B, et al. Control of PI(3) kinase in Treg cells maintains homeostasis and lineage stability. Nat Immunol. 2015;16:188\u201396.","journal-title":"Nat Immunol"},{"key":"5_CR59","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41422-020-0324-7","volume":"30","author":"N Ohkura","year":"2020","unstructured":"Ohkura N, Sakaguchi S. Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases. Cell Res. 2020;30:465\u201374.","journal-title":"Cell Res"},{"key":"5_CR60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050038","volume":"5","author":"S Floess","year":"2007","unstructured":"Floess S, Freyer J, Siewert C, et al. Epigenetic control of the foxp3 locus in regulatory T cells. PLoS Biol. 2007;5:e38.","journal-title":"PLoS Biol"},{"key":"5_CR61","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/ni.3646","volume":"18","author":"Y Kitagawa","year":"2017","unstructured":"Kitagawa Y, Ohkura N, Kidani Y, et al. Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment. Nat Immunol. 2017;18:173\u201383.","journal-title":"Nat Immunol"},{"key":"5_CR62","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1038\/nature08750","volume":"463","author":"Y Zheng","year":"2010","unstructured":"Zheng Y, Josefowicz S, Chaudhry A, et al. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature. 2010;463:808\u201312.","journal-title":"Nature"},{"key":"5_CR63","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.cell.2014.07.031","volume":"158","author":"Y Feng","year":"2014","unstructured":"Feng Y, Arvey A, Chinen T, et al. Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus. Cell. 2014;158:749\u201363.","journal-title":"Cell"},{"key":"5_CR64","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1016\/j.cell.2014.07.030","volume":"158","author":"X Li","year":"2014","unstructured":"Li X, Liang Y, LeBlanc M, et al. Function of a Foxp3 cis-element in protecting regulatory T cell identity. Cell. 2014;158:734\u201348.","journal-title":"Cell"},{"key":"5_CR65","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1093\/intimm\/dxz008","volume":"31","author":"H Nakatsukasa","year":"2019","unstructured":"Nakatsukasa H, Oda M, Yin J, et al. Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization and IL-17 expression. Int Immunol. 2019;31:335\u201347.","journal-title":"Int Immunol"},{"key":"5_CR66","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1038\/s41467-019-09541-y","volume":"10","author":"X Yue","year":"2019","unstructured":"Yue X, Lio CWJ, Samaniego-Castruita D, et al. Loss of TET2 and TET3 in regulatory T cells unleashes effector function. Nat Commun. 2019;10:2011. https:\/\/doi.org\/10.1038\/s41467-019-09541-y.","journal-title":"Nat Commun"},{"key":"5_CR67","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1084\/jem.20151438","volume":"213","author":"X Yue","year":"2016","unstructured":"Yue X, Trifari S, \u00c4ij\u00f6 T, et al. Control of Foxp3 stability through modulation of TET activity. J Exp Med. 2016;213:377\u201397.","journal-title":"J Exp Med"},{"key":"5_CR68","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/j.immuni.2012.09.010","volume":"37","author":"N Ohkura","year":"2012","unstructured":"Ohkura N, Hamaguchi M, Morikawa H, et al. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity. 2012;37:785\u201399.","journal-title":"Immunity"},{"key":"5_CR69","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/imr.12532","volume":"277","author":"SR Daley","year":"2017","unstructured":"Daley SR, Teh C, Hu DY, et al. Cell death and thymic tolerance. Immunol Rev. 2017;277:9.","journal-title":"Immunol Rev"},{"key":"5_CR70","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/ni1318","volume":"7","author":"CS Hsieh","year":"2006","unstructured":"Hsieh CS, Zheng Y, Liang Y, et al. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat Immunol. 2006;7:401\u201310.","journal-title":"Nat Immunol"},{"key":"5_CR71","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41577-018-0083-6","volume":"19","author":"L Klein","year":"2019","unstructured":"Klein L, Robey EA, Hsieh C-S. Central CD4+ T cell tolerance: deletion versus regulatory T cell differentiation. Nat Rev Immunol. 2019;19:7\u201318.","journal-title":"Nat Rev Immunol"},{"key":"5_CR72","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.immuni.2006.05.016","volume":"25","author":"R Pacholczyk","year":"2006","unstructured":"Pacholczyk R, Ignatowicz H, Kraj P, Ignatowicz L. Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells. Immunity. 2006;25:249\u201359.","journal-title":"Immunity"},{"key":"5_CR73","doi-asserted-by":"publisher","first-page":"3180","DOI":"10.4049\/jimmunol.1203473","volume":"190","author":"A Toker","year":"2013","unstructured":"Toker A, Engelbert D, Garg G, et al. Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus. J Immunol. 2013;190:3180\u20138.","journal-title":"J Immunol"},{"key":"5_CR74","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1016\/j.immuni.2021.04.005","volume":"54","author":"R Kawakami","year":"2021","unstructured":"Kawakami R, Kitagawa Y, Chen KY, et al. Distinct Foxp3 enhancer elements coordinate development, maintenance, and function of regulatory T cells. Immunity. 2021;54:947. https:\/\/doi.org\/10.1016\/j.immuni.2021.04.005.","journal-title":"Immunity"},{"key":"5_CR75","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1084\/jem.20110308","volume":"208","author":"AE Moran","year":"2011","unstructured":"Moran AE, Holzapfel KL, Xing Y, et al. T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. J Exp Med. 2011;208:1279\u201389.","journal-title":"J Exp Med"},{"key":"5_CR76","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/nature11311","volume":"489","author":"J Zikherman","year":"2012","unstructured":"Zikherman J, Parameswaran R, Weiss A. Endogenous antigen tunes the responsiveness of naive B cells but not T cells. Nature. 2012;489:160\u20134.","journal-title":"Nature"},{"key":"5_CR77","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1016\/j.immuni.2013.02.022","volume":"38","author":"X Tai","year":"2013","unstructured":"Tai X, Erman B, Alag A, et al. Foxp3 transcription factor is proapoptotic and lethal to developing regulatory T cells unless counterbalanced by cytokine survival signals. Immunity. 2013;38:1116\u201328.","journal-title":"Immunity"},{"key":"5_CR78","doi-asserted-by":"publisher","first-page":"11903","DOI":"10.1073\/pnas.0801506105","volume":"105","author":"A Liston","year":"2008","unstructured":"Liston A, Nutsch KM, Farr AG, et al. Differentiation of regulatory Foxp3+ T cells in the thymic cortex. Proc Natl Acad Sci U S A. 2008;105:11903\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"5_CR79","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/ni1444","volume":"8","author":"K Aschenbrenner","year":"2007","unstructured":"Aschenbrenner K, D\u2019Cruz LM, Vollmann EH, et al. Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells. Nat Immunol. 2007;8(4):351\u20138.","journal-title":"Nat Immunol"},{"key":"5_CR80","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1016\/j.immuni.2016.02.009","volume":"44","author":"S Malchow","year":"2016","unstructured":"Malchow S, Leventhal DS, Lee V, et al. Aire enforces immune tolerance by directing autoreactive T cells into the regulatory T cell lineage. Immunity. 2016;44:1102\u201313.","journal-title":"Immunity"},{"key":"5_CR81","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/J.IT.2022.07.010","volume":"43","author":"DA Michelson","year":"2022","unstructured":"Michelson DA, Mathis D. Thymic mimetic cells: tolerogenic masqueraders. Trends Immunol. 2022;43:782. https:\/\/doi.org\/10.1016\/J.IT.2022.07.010.","journal-title":"Trends Immunol"},{"key":"5_CR82","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2215474119","volume":"119","author":"DA Michelson","year":"2022","unstructured":"Michelson DA, Benoist C, Mathis D. CTLA-4 on thymic epithelial cells complements Aire for T cell central tolerance. Proc Natl Acad Sci U S A. 2022;119:e2215474119.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"5_CR83","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110384","volume":"38","author":"J Morimoto","year":"2022","unstructured":"Morimoto J, Matsumoto M, Miyazawa R, et al. Aire suppresses CTLA-4 expression from the thymic stroma to control autoimmunity. Cell Rep. 2022;38:110384.","journal-title":"Cell Rep"},{"key":"5_CR84","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.immuni.2007.11.021","volume":"28","author":"CWJ Lio","year":"2008","unstructured":"Lio CWJ, Hsieh CS. A two-step process for thymic regulatory T cell development. Immunity. 2008;28:100\u201311.","journal-title":"Immunity"},{"key":"5_CR85","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/s41590-018-0289-6","volume":"20","author":"DL Owen","year":"2019","unstructured":"Owen DL, Mahmud SA, Sjaastad LE, et al. Thymic regulatory T cells arise via two distinct developmental programs. Nat Immunol. 2019;20:195. https:\/\/doi.org\/10.1038\/s41590-018-0289-6.","journal-title":"Nat Immunol"},{"key":"5_CR86","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.immuni.2007.11.022","volume":"28","author":"AM Burchill","year":"2008","unstructured":"Burchill AM, Yang J, Vang BK, et al. Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire. Immunity. 2008;28:112\u201321.","journal-title":"Immunity"},{"key":"5_CR87","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/ni.2849","volume":"15","author":"SA Mahmud","year":"2014","unstructured":"Mahmud SA, Manlove LS, Schmitz HM, et al. Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells. Nat Immunol. 2014;15:473\u201381.","journal-title":"Nat Immunol"},{"key":"5_CR88","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1016\/j.celrep.2018.07.008","volume":"24","author":"T Sekiya","year":"2018","unstructured":"Sekiya T, Hibino S, Saeki K, et al. Nr4a receptors regulate development and death of labile Treg precursors to prevent generation of pathogenic self-reactive cells. Cell Rep. 2018;24:1627\u20131638.e6.","journal-title":"Cell Rep"},{"key":"5_CR89","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/ni.2520","volume":"14","author":"T Sekiya","year":"2013","unstructured":"Sekiya T, Kashiwagi I, Yoshida R, et al. Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis. Nat Immunol. 2013;14:230. https:\/\/doi.org\/10.1038\/ni.2520.","journal-title":"Nat Immunol"},{"key":"5_CR90","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/s41590-023-01469-2","volume":"24","author":"X Tai","year":"2023","unstructured":"Tai X, Indart A, Rojano M, et al. How autoreactive thymocytes differentiate into regulatory versus effector CD4+ T cells after avoiding clonal deletion. Nat Immunol. 2023;24:637\u201351.","journal-title":"Nat Immunol"},{"key":"5_CR91","doi-asserted-by":"publisher","first-page":"920","DOI":"10.4049\/jimmunol.1600877","volume":"199","author":"M Schuster","year":"2017","unstructured":"Schuster M, Plaza-Sirvent C, Matthies A-M, et al. C-REL and I\u03baBNS govern common and independent steps of regulatory T cell development from novel CD122-expressing pre-precursors. J Immunol. 2017;199:920\u201330.","journal-title":"J Immunol"},{"key":"5_CR92","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.4049\/jimmunol.2200089","volume":"209","author":"DL Owen","year":"2022","unstructured":"Owen DL, La Rue RS, Munro SA, Farrar MA. Tracking regulatory T cell development in the thymus using single-cell RNA sequencing\/TCR sequencing. J Immunol. 2022;209:1300\u201313.","journal-title":"J Immunol"},{"key":"5_CR93","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/nature16141","volume":"528","author":"Y Feng","year":"2015","unstructured":"Feng Y, van der Veeken J, Shugay M, et al. A mechanism for expansion of regulatory T-cell repertoire and its role in self-tolerance. Nature. 2015;528:132\u20136.","journal-title":"Nature"},{"key":"5_CR94","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1038\/ni.3812","volume":"18","author":"K Placek","year":"2017","unstructured":"Placek K, Hu G, Cui K, et al. MLL4 prepares the enhancer landscape for Foxp3 induction via chromatin looping. Nat Immunol. 2017;18:1035\u201345.","journal-title":"Nat Immunol"},{"key":"5_CR95","doi-asserted-by":"publisher","first-page":"eaaw2707","DOI":"10.1126\/sciimmunol.aaw2707","volume":"4","author":"M Akamatsu","year":"2019","unstructured":"Akamatsu M, Mikami N, Ohkura N, et al. Conversion of antigen-specific effector\/memory T cells into Foxp3-expressing Treg cells by inhibition of CDK8\/19. Sci Immunol. 2019;4:eaaw2707.","journal-title":"Sci Immunol"},{"key":"5_CR96","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/j.immuni.2021.03.020","volume":"54","author":"S Dikiy","year":"2021","unstructured":"Dikiy S, Li J, Bai L, et al. A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance. Immunity. 2021;54:931. https:\/\/doi.org\/10.1016\/j.immuni.2021.03.020.","journal-title":"Immunity"},{"key":"5_CR97","doi-asserted-by":"publisher","first-page":"e20202415","DOI":"10.1084\/jem.20202415","volume":"218","author":"X Zong","year":"2021","unstructured":"Zong X, Hao X, Xu B, et al. Foxp3 enhancers synergize to maximize regulatory T cell suppressive capacity. J Exp Med. 2021;218:e20202415. https:\/\/doi.org\/10.1084\/jem.20202415.","journal-title":"J Exp Med"},{"key":"5_CR98","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.it.2016.08.012","volume":"37","author":"M Kanamori","year":"2016","unstructured":"Kanamori M, Nakatsukasa H, Okada M, et al. Induced regulatory T cells: their development, stability, and applications. Trends Immunol. 2016;37:803\u201311.","journal-title":"Trends Immunol"},{"key":"5_CR99","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41577-023-00890-w","volume":"23","author":"D Ramanan","year":"2023","unstructured":"Ramanan D, Pratama A, Zhu Y, et al. Regulatory T cells in the face of the intestinal microbiota. Nat Rev Immunol. 2023;23:749. https:\/\/doi.org\/10.1038\/s41577-023-00890-w.","journal-title":"Nat Rev Immunol"},{"key":"5_CR100","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1126\/science.1198469","volume":"331","author":"K Atarashi","year":"2011","unstructured":"Atarashi K, Tanoue T, Shima T, et al. Induction of colonic regulatory T cells by indigenous clostridium species. Science. 2011;331:337. https:\/\/doi.org\/10.1126\/science.1198469.","journal-title":"Science"},{"key":"5_CR101","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1126\/science.aac5560","volume":"351","author":"KS Kim","year":"2016","unstructured":"Kim KS, Hong SW, Han D, et al. Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science. 2016;351:858. https:\/\/doi.org\/10.1126\/science.aac5560.","journal-title":"Science"},{"key":"5_CR102","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/nature10434","volume":"478","author":"SK Lathrop","year":"2011","unstructured":"Lathrop SK, Bloom SM, Rao SM, et al. Peripheral education of the immune system by colonic commensal microbiota. Nature. 2011;478:250\u20134.","journal-title":"Nature"},{"key":"5_CR103","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.cell.2012.05.031","volume":"150","author":"RM Samstein","year":"2012","unstructured":"Samstein RM, Josefowicz SZ, Arvey A, et al. Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict. Cell. 2012;150:29. https:\/\/doi.org\/10.1016\/j.cell.2012.05.031.","journal-title":"Cell"},{"key":"5_CR104","doi-asserted-by":"publisher","first-page":"3926","DOI":"10.4049\/jimmunol.1800097","volume":"200","author":"DL Owen","year":"2018","unstructured":"Owen DL, Mahmud SA, Vang KB, et al. Identification of cellular sources of IL-2 needed for regulatory T cell development and homeostasis. J Immunol. 2018;200:3926\u201333.","journal-title":"J Immunol"},{"key":"5_CR105","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/s41586-019-1082-x","volume":"568","author":"L Zhou","year":"2019","unstructured":"Zhou L, Chu C, Teng F, et al. Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2. Nature. 2019;568:405\u20139.","journal-title":"Nature"},{"key":"5_CR106","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/mi.2010.7","volume":"3","author":"L Xu","year":"2010","unstructured":"Xu L, Kitani A, Strober W. Molecular mechanisms regulating TGF-beta-induced Foxp3 expression. Mucosal Immunol. 2010;3:230\u20138.","journal-title":"Mucosal Immunol"},{"key":"5_CR107","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41586-020-2193-0","volume":"581","author":"C Campbell","year":"2020","unstructured":"Campbell C, McKenney PT, Konstantinovsky D, et al. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature. 2020;581:1\u20135.","journal-title":"Nature"},{"key":"5_CR108","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41586-019-1785-z","volume":"576","author":"S Hang","year":"2019","unstructured":"Hang S, Paik D, Yao L, et al. Bile acid metabolites control TH17 and Treg cell differentiation. Nature. 2019;576:143\u20138.","journal-title":"Nature"},{"key":"5_CR109","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/s41586-019-1865-0","volume":"577","author":"X Song","year":"2020","unstructured":"Song X, Sun X, Oh SF, et al. Microbial bile acid metabolites modulate gut ROR\u03b3+ regulatory T cell homeostasis. Nature. 2020;577:410\u20135.","journal-title":"Nature"},{"key":"5_CR110","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nri.2016.36","volume":"16","author":"T Tanoue","year":"2016","unstructured":"Tanoue T, Atarashi K, Honda K. Development and maintenance of intestinal regulatory T cells. Nat Rev Immunol. 2016;16:295\u2013309.","journal-title":"Nat Rev Immunol"},{"key":"5_CR111","doi-asserted-by":"publisher","first-page":"3433","DOI":"10.4049\/jimmunol.0904028","volume":"184","author":"AM Thornton","year":"2010","unstructured":"Thornton AM, Korty PE, Tran DQ, et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol. 2010;184:3433\u201341.","journal-title":"J Immunol"},{"key":"5_CR112","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1084\/jem.20120822","volume":"209","author":"M Yadav","year":"2012","unstructured":"Yadav M, Louvet C, Davini D, et al. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J Exp Med. 2012;209:1713\u201322.","journal-title":"J Exp Med"},{"key":"5_CR113","doi-asserted-by":"publisher","first-page":"976","DOI":"10.4049\/jimmunol.1102964","volume":"188","author":"RA Gottschalk","year":"2012","unstructured":"Gottschalk RA, Corse E, Allison JP. Expression of Helios in peripherally induced Foxp3+ regulatory T cells. J Immunol. 2012;188:976\u201380.","journal-title":"J Immunol"},{"key":"5_CR114","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/ni.1607","volume":"9","author":"Y Liu","year":"2008","unstructured":"Liu Y, Zhang P, Li J, et al. A critical function for TGF-\u03b2 signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells. Nat Immunol. 2008;9:632\u201340.","journal-title":"Nat Immunol"},{"key":"5_CR115","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1084\/jem.20042276","volume":"201","author":"JC Marie","year":"2005","unstructured":"Marie JC, Letterio JJ, Gavin M, Rudensky AY. TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med. 2005;201:1061\u20137.","journal-title":"J Exp Med"},{"key":"5_CR116","doi-asserted-by":"publisher","first-page":"eabe4723","DOI":"10.1126\/SCIIMMUNOL.ABE4723","volume":"6","author":"S Junius","year":"2021","unstructured":"Junius S, Mavrogiannis AV, Lemaitre P, et al. Unstable regulatory T cells, enriched for na\u00efve and Nrp1neg cells, are purged after fate challenge. Sci Immunol. 2021;6:eabe4723. https:\/\/doi.org\/10.1126\/SCIIMMUNOL.ABE4723.","journal-title":"Sci Immunol"},{"key":"5_CR117","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1146\/annurev.immunol.21.120601.141040","volume":"21","author":"RM Steinman","year":"2003","unstructured":"Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol. 2003;21:685\u2013711.","journal-title":"Annu Rev Immunol"},{"key":"5_CR118","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41586-022-04916-6","volume":"607","author":"S-W Hong","year":"2022","unstructured":"Hong S-W, Krueger PD, Osum KC, et al. Immune tolerance of food is mediated by layers of CD4+ T cell dysfunction. Nature. 2022;607:1\u20137.","journal-title":"Nature"},{"key":"5_CR119","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.4049\/jimmunol.1602031","volume":"198","author":"LA Kalekar","year":"2017","unstructured":"Kalekar LA, Mueller DL. Relationship between CD4 regulatory T cells and anergy in vivo. J Immunol. 2017;198:2527\u201333.","journal-title":"J Immunol"},{"key":"5_CR120","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/ni.3331","volume":"17","author":"LA Kalekar","year":"2016","unstructured":"Kalekar LA, Schmiel SE, Nandiwada SL, et al. CD4+ T cell anergy prevents autoimmunity and generates regulatory T cell precursors. Nat Immunol. 2016;17:304\u201314.","journal-title":"Nat Immunol"},{"key":"5_CR121","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.it.2022.12.006","volume":"44","author":"J Bourque","year":"2023","unstructured":"Bourque J, Hawiger D. Life and death of tolerogenic dendritic cells. Trends Immunol. 2023;44:110\u20138.","journal-title":"Trends Immunol"},{"key":"5_CR122","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1084\/jem.20040662","volume":"202","author":"O Annacker","year":"2005","unstructured":"Annacker O, Coombes JL, Malmstrom V, et al. Essential role for CD103 in the T cell-mediated regulation of experimental colitis. J Exp Med. 2005;202:1051\u201361.","journal-title":"J Exp Med"},{"key":"5_CR123","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1084\/jem.20070590","volume":"204","author":"JL Coombes","year":"2007","unstructured":"Coombes JL, Siddiqui KRR, Arancibia-C\u00e1rcamo CV, et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med. 2007;204:1757\u201364.","journal-title":"J Exp Med"},{"key":"5_CR124","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/ni.3408","volume":"17","author":"D Esterh\u00e1zy","year":"2016","unstructured":"Esterh\u00e1zy D, Loschko J, London M, et al. Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T reg cells and tolerance. Nat Immunol. 2016;17:545\u201355.","journal-title":"Nat Immunol"},{"key":"5_CR125","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1084\/jem.20070602","volume":"204","author":"CM Sun","year":"2007","unstructured":"Sun CM, Hall JA, Blank RB, et al. Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med. 2007;204:1775\u201385.","journal-title":"J Exp Med"},{"key":"5_CR126","doi-asserted-by":"publisher","first-page":"4293","DOI":"10.1182\/blood-2007-05-088831","volume":"110","author":"S Yamazaki","year":"2007","unstructured":"Yamazaki S, Bonito AJ, Spisek R, et al. Dendritic cells are specialized accessory cells along with TGF- for the differentiation of Foxp3+ CD4+ regulatory T cells from peripheral Foxp3 precursors. Blood. 2007;110:4293\u2013302.","journal-title":"Blood"},{"key":"5_CR127","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/mi.2016.46","volume":"10","author":"Y Tanaka","year":"2017","unstructured":"Tanaka Y, Nagashima H, Bando K, et al. Oral CD103 - CD11b + classical dendritic cells present sublingual antigen and induce Foxp3 + regulatory T cells in draining lymph nodes. Mucosal Immunol. 2017;10:79. https:\/\/doi.org\/10.1038\/mi.2016.46.","journal-title":"Mucosal Immunol"},{"key":"5_CR128","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41586-022-05309-5","volume":"610","author":"B Akagbosu","year":"2022","unstructured":"Akagbosu B, Tayyebi Z, Shibu G, et al. Novel antigen presenting cell imparts Treg-dependent tolerance to gut microbiota. Nature. 2022;610:1\u20133.","journal-title":"Nature"},{"key":"5_CR129","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41586-022-05089-y","volume":"610","author":"R Kedmi","year":"2022","unstructured":"Kedmi R, Najar TA, Mesa KR, et al. A ROR\u03b3t+ cell instructs gut microbiota-specific Treg cell differentiation. Nature. 2022;610:1\u20137.","journal-title":"Nature"},{"key":"5_CR130","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41586-022-05141-x","volume":"610","author":"M Lyu","year":"2022","unstructured":"Lyu M, Suzuki H, Kang L, et al. ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut. Nature. 2022;610:1\u20138.","journal-title":"Nature"},{"key":"5_CR131","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/j.immuni.2023.03.008","volume":"56","author":"A Weckel","year":"2023","unstructured":"Weckel A, Dhariwala MO, Ly K, et al. Long-term tolerance to skin commensals is established neonatally through a specialized dendritic cell subgroup. Immunity. 2023;56:1239\u20131254.e7.","journal-title":"Immunity"},{"key":"5_CR132","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1084\/jem.20112646","volume":"209","author":"SM Schlenner","year":"2012","unstructured":"Schlenner SM, Weigmann B, Ruan Q, et al. Smad3 binding to the foxp3 enhancer is dispensable for the development of regulatory T cells with the exception of the gut. J Exp Med. 2012;209:1529. https:\/\/doi.org\/10.1084\/jem.20112646.","journal-title":"J Exp Med"},{"key":"5_CR133","doi-asserted-by":"publisher","first-page":"6007","DOI":"10.4049\/jimmunol.1000019","volume":"184","author":"C-WJ Lio","year":"2010","unstructured":"Lio C-WJ, Dodson LF, Deppong CM, et al. CD28 facilitates the generation of Foxp3\u2212 cytokine responsive regulatory T cell precursors. J Immunol. 2010;184:6007\u201313.","journal-title":"J Immunol"},{"key":"5_CR134","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1093\/intimm\/dxy013","volume":"30","author":"E Wakamatsu","year":"2018","unstructured":"Wakamatsu E, Omori H, Tabata Y, et al. CD28 co-stimulation is dispensable for the steady state homeostasis of intestinal regulatory T cells. Int Immunol. 2018;30:171\u201380.","journal-title":"Int Immunol"},{"key":"5_CR135","doi-asserted-by":"publisher","first-page":"12258","DOI":"10.1073\/pnas.1922600117","volume":"117","author":"N Mikami","year":"2020","unstructured":"Mikami N, Kawakami R, Chen KY, et al. Epigenetic conversion of conventional T cells into regulatory T cells by CD28 signal deprivation. Proc Natl Acad Sci. 2020a;117:12258\u201368.","journal-title":"Proc Natl Acad Sci"},{"key":"5_CR136","doi-asserted-by":"publisher","first-page":"3096","DOI":"10.1182\/blood-2010-08-301275","volume":"117","author":"K Semple","year":"2011","unstructured":"Semple K, Nguyen A, Yu Y, et al. Strong CD28 costimulation suppresses induction of regulatory T cells from naive precursors through Lck signaling. Blood. 2011;117:3096\u2013103.","journal-title":"Blood"},{"key":"5_CR137","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41573-019-0041-4","volume":"18","author":"LMR Ferreira","year":"2019","unstructured":"Ferreira LMR, Muller YD, Bluestone JA, Tang Q. Next-generation regulatory T cell therapy. Nat Rev Drug Discov. 2019;18:749.","journal-title":"Nat Rev Drug Discov"},{"key":"5_CR138","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/s41577-019-0232-6","volume":"20","author":"C Raffin","year":"2020","unstructured":"Raffin C, Vo LT, Bluestone JA. Treg cell-based therapies: challenges and perspectives. Nat Rev Immunol. 2020;20:158\u201372.","journal-title":"Nat Rev Immunol"},{"key":"5_CR139","doi-asserted-by":"publisher","first-page":"ltad007","DOI":"10.1093\/immadv\/ltad007","volume":"3","author":"S Sakaguchi","year":"2023","unstructured":"Sakaguchi S, Kawakami R, Mikami N. Treg-based immunotherapy for antigen-specific immune suppression and stable tolerance induction: a perspective. Immunother Adv. 2023;3:ltad007. https:\/\/doi.org\/10.1093\/immadv\/ltad007.","journal-title":"Immunother Adv"},{"key":"5_CR140","doi-asserted-by":"publisher","first-page":"e20191247","DOI":"10.1084\/jem.20191247","volume":"217","author":"JG Pol","year":"2020","unstructured":"Pol JG, Caudana P, Paillet J, et al. Effects of interleukin-2 in immunostimulation and immunosuppression. J Exp Med. 2020;217:e20191247. https:\/\/doi.org\/10.1084\/jem.20191247.","journal-title":"J Exp Med"},{"key":"5_CR141","doi-asserted-by":"publisher","first-page":"2749","DOI":"10.4049\/jimmunol.1900733","volume":"203","author":"M Tahvildari","year":"2019","unstructured":"Tahvildari M, Dana R. Low-dose IL-2 therapy in transplantation, autoimmunity, and inflammatory diseases. J Immunol. 2019;203:2749\u201355.","journal-title":"J Immunol"},{"key":"5_CR142","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/BOR.0000000000000924","volume":"35","author":"R Akbarzadeh","year":"2023","unstructured":"Akbarzadeh R, Riemekasten G, Humrich JY. Low-dose interleukin-2 therapy: a promising targeted therapeutic approach for systemic lupus erythematosus. Curr Opin Rheumatol. 2023;35:98\u2013106.","journal-title":"Curr Opin Rheumatol"},{"key":"5_CR143","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1093\/cei\/uxac105","volume":"211","author":"F Harris","year":"2023","unstructured":"Harris F, Berdugo YA, Tree T. IL-2-based approaches to Treg enhancement. Clin Exp Immunol. 2023;211:149. https:\/\/doi.org\/10.1093\/cei\/uxac105.","journal-title":"Clin Exp Immunol"},{"key":"5_CR144","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.713358","volume":"12","author":"S Ikegawa","year":"2021","unstructured":"Ikegawa S, Matsuoka K-I. Harnessing Treg homeostasis to optimize posttransplant immunity: current concepts and future perspectives. Front Immunol. 2021;12:713358.","journal-title":"Front Immunol"},{"key":"5_CR145","doi-asserted-by":"publisher","first-page":"eaba5264","DOI":"10.1126\/SCIIMMUNOL.ABA5264","volume":"5","author":"L Khoryati","year":"2020","unstructured":"Khoryati L, Pham MN, Sherve M, et al. An IL-2 mutein engineered to promote expansion of regulatory T cells arrests ongoing autoimmunity in mice. Sci Immunol. 2020;5:eaba5264. https:\/\/doi.org\/10.1126\/SCIIMMUNOL.ABA5264.","journal-title":"Sci Immunol"},{"key":"5_CR146","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/s41591-018-0070-2","volume":"24","author":"E Trotta","year":"2018","unstructured":"Trotta E, Bessette PH, Silveria SL, et al. A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism. Nat Med. 2018;24:1005\u201314.","journal-title":"Nat Med"},{"key":"5_CR147","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtauto.2021.100103","volume":"4","author":"N Dixit","year":"2021","unstructured":"Dixit N, Fanton C, Langowski JL, et al. NKTR-358: a novel regulatory T-cell stimulator that selectively stimulates expansion and suppressive function of regulatory T cells for the treatment of autoimmune and inflammatory diseases. J Transl Autoimmun. 2021;4:100103.","journal-title":"J Transl Autoimmun"},{"key":"5_CR148","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1126\/science.1122927","volume":"311","author":"O Boyman","year":"2006","unstructured":"Boyman O, Kovar M, Rubinstein MP, et al. Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science. 2006;311:1924\u20137.","journal-title":"Science"},{"key":"5_CR149","doi-asserted-by":"publisher","first-page":"eabb9283","DOI":"10.1126\/scitranslmed.abb9283","volume":"12","author":"U Karakus","year":"2020","unstructured":"Karakus U, Sahin D, Mittl PRE, et al. Receptor-gated IL-2 delivery by an anti-human IL-2 antibody activates regulatory T cells in three different species. Sci Transl Med. 2020;12:eabb9283. https:\/\/doi.org\/10.1126\/scitranslmed.abb9283.","journal-title":"Sci Transl Med"},{"key":"5_CR150","doi-asserted-by":"publisher","first-page":"6757","DOI":"10.1038\/s41467-022-34477-1","volume":"13","author":"CJ Wang","year":"2022","unstructured":"Wang CJ, Petersone L, Edner NM, et al. Costimulation blockade in combination with IL-2 permits regulatory T cell sparing immunomodulation that inhibits autoimmunity. Nat Commun. 2022;13:6757.","journal-title":"Nat Commun"},{"key":"5_CR151","doi-asserted-by":"publisher","first-page":"2340","DOI":"10.2337\/db12-0049","volume":"61","author":"SA Long","year":"2012","unstructured":"Long SA, Rieck M, Sanda S, et al. Rapamycin\/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs \u03b2-cell function. Diabetes. 2012;61:2340\u20138.","journal-title":"Diabetes"},{"key":"5_CR152","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.coi.2020.07.004","volume":"67","author":"N Mikami","year":"2020","unstructured":"Mikami N, Kawakami R, Sakaguchi S. New Treg cell-based therapies of autoimmune diseases: towards antigen-specific immune suppression. Curr Opin Immunol. 2020b;67:36\u201341.","journal-title":"Curr Opin Immunol"},{"key":"5_CR153","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.4049\/jimmunol.1502352","volume":"196","author":"V Sasidharan Nair","year":"2016","unstructured":"Sasidharan Nair V, Song MH, Oh KI. Vitamin C facilitates demethylation of the Foxp3 enhancer in a Tet-dependent manner. J Immunol. 2016;196:2119\u201331.","journal-title":"J Immunol"},{"key":"5_CR154","doi-asserted-by":"publisher","first-page":"8742","DOI":"10.1073\/pnas.0911756107","volume":"107","author":"B-S Kim","year":"2010","unstructured":"Kim B-S, Kim I-K, Park Y-J, et al. Conversion of Th2 memory cells into Foxp3+ regulatory T cells suppressing Th2-mediated allergic asthma. Proc Natl Acad Sci. 2010;107:8742\u20137.","journal-title":"Proc Natl Acad Sci"},{"key":"5_CR155","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1093\/intimm\/dxy043","volume":"30","author":"M Kanamori","year":"2018","unstructured":"Kanamori M, Nakatsukasa H, Ito M, et al. Reprogramming of Th1 cells into regulatory T cells through rewiring of the metabolic status. Int Immunol. 2018;30:357\u201373.","journal-title":"Int Immunol"},{"key":"5_CR156","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/j.tibtech.2019.12.009","volume":"38","author":"E Fritsche","year":"2020","unstructured":"Fritsche E, Volk H-D, Reinke P, Abou-El-Enein M. Toward an optimized process for clinical manufacturing of CAR-Treg cell therapy. Trends Biotechnol. 2020;38:1099\u2013112.","journal-title":"Trends Biotechnol"},{"key":"5_CR157","doi-asserted-by":"publisher","first-page":"1608","DOI":"10.3389\/fimmu.2020.01608","volume":"11","author":"YR Mohseni","year":"2020","unstructured":"Mohseni YR, Tung SL, Dudreuilh C, et al. The future of regulatory T cell therapy: promises and challenges of implementing CAR technology. Front Immunol. 2020;11:1608.","journal-title":"Front Immunol"},{"key":"5_CR158","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1111\/ajt.14185","volume":"17","author":"DA Boardman","year":"2017","unstructured":"Boardman DA, Philippeos C, Fruhwirth GO, et al. Expression of a chimeric antigen receptor specific for donor HLA class I enhances the potency of human regulatory T cells in preventing human skin transplant rejection. Am J Transplant. 2017;17:931\u201343.","journal-title":"Am J Transplant"},{"key":"5_CR159","doi-asserted-by":"publisher","first-page":"e160674","DOI":"10.1172\/jci.insight.160674","volume":"7","author":"S Bolivar-Wagers","year":"2022","unstructured":"Bolivar-Wagers S, Loschi ML, Jin S, et al. Murine CAR19 Tregs suppress acute graft-versus-host disease and maintain graft-versus-tumor responses. JCI Insight. 2022;7:e160674. https:\/\/doi.org\/10.1172\/jci.insight.160674.","journal-title":"JCI Insight"}],"container-title":["Advances in Experimental Medicine and Biology","Basic Immunology and Its Clinical Application"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/978-981-99-9781-7_5","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T06:09:58Z","timestamp":1710223798000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/978-981-99-9781-7_5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024]]},"ISBN":["9789819997800","9789819997817"],"references-count":159,"URL":"https:\/\/doi.org\/10.1007\/978-981-99-9781-7_5","relation":{},"ISSN":["0065-2598","2214-8019"],"issn-type":[{"value":"0065-2598","type":"print"},{"value":"2214-8019","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024]]},"assertion":[{"value":"12 March 2024","order":1,"name":"first_online","label":"First Online","group":{"name":"ChapterHistory","label":"Chapter History"}}]}}