{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T12:25:42Z","timestamp":1794313542279,"version":"4.9.0"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Regulatory T cells in non-lymphoid tissues are not only critical for maintaining self-tolerance, but are also important for promoting organ homeostasis and tissue repair. It is proposed that the generation of tissue Treg cells is a stepwise, multi-site process, accompanied by extensive epigenome remodeling, finally leading to the acquisition of unique tissue-specific epigenetic signatures. This process is initiated in the thymus, where Treg cells acquire core phenotypic and functional properties, followed by a priming step in secondary lymphoid organs that permits Treg cells to exit the lymphoid organs and seed into non-lymphoid tissues. There, a final specialization process takes place in response to unique microenvironmental cues in the respective tissue. In this review, we will summarize recent findings on this multi-site tissue Treg cell differentiation and highlight the importance of epigenetic remodeling during these stepwise events.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1082055","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T04:52:55Z","timestamp":1670475175000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Stepwise acquisition of unique epigenetic signatures during differentiation of tissue Treg cells"],"prefix":"10.3389","volume":"13","author":[{"given":"Kathrin L.","family":"Braband","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Kaufmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Floess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mangge","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Huehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Delacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ni904","article-title":"Foxp3 programs the development and function of CD4+CD25+ regulatory T cells","volume":"4","author":"Fontenot","year":"2003","journal-title":"Nat Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079490","article-title":"Control of regulatory T cell development by the transcription factor Foxp3","volume":"299","author":"Hori","year":"2003","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/83784","article-title":"Disruption of a new forkhead\/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse","volume":"27","author":"Brunkow","year":"2001","journal-title":"Nat Genet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/83707","article-title":"X-Linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy","volume":"27","author":"Wildin","year":"2001","journal-title":"Nat Genet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/83713","article-title":"The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3","volume":"27","author":"Bennett","year":"2001","journal-title":"Nat Genet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/ni909","article-title":"An essential role for scurfin in CD4+CD25+ T regulatory cells","volume":"4","author":"Khattri","year":"2003","journal-title":"Nat Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/ni1437","article-title":"Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3","volume":"8","author":"Williams","year":"2007","journal-title":"Nat Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0050038","article-title":"Epigenetic control of the foxp3 locus in regulatory T cells","volume":"5","author":"Floess","year":"2007","journal-title":"PloS Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nri2474","article-title":"Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage","volume":"9","author":"Huehn","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxl060","article-title":"Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis","volume":"18","author":"Sugimoto","year":"2006","journal-title":"Int Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1016\/j.immuni.2007.09.010","article-title":"Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature","volume":"27","author":"Hill","year":"2007","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070109","article-title":"CREB\/ATF-dependent T cell receptor-induced FoxP3 gene expression: A role for DNA methylation","volume":"204","author":"Kim","year":"2007","journal-title":"J Exp Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.09.010","article-title":"T Cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for treg cell development","volume":"37","author":"Ohkura","year":"2012","journal-title":"Immunity"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203473","article-title":"Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus","volume":"190","author":"Toker","year":"2013","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095948","article-title":"Tissue tregs","volume":"34","author":"Panduro","year":"2016","journal-title":"Annu Rev Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.954798","article-title":"Implications of regulatory T cells in non-lymphoid tissue physiology and pathophysiology","volume":"13","author":"Malko","year":"2022","journal-title":"Front Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nature11132","article-title":"PPAR-gamma is a major driver of the accumulation and phenotype of adipose tissue treg cells","volume":"486","author":"Cipolletta","year":"2012","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2002","article-title":"Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters","volume":"15","author":"Feuerer","year":"2009","journal-title":"Nat Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3085","article-title":"The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells","volume":"16","author":"Vasanthakumar","year":"2015","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.cell.2017.05.002","article-title":"Regulatory T cells in skin facilitate epithelial stem cell differentiation","volume":"169","author":"Ali","year":"2017","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nature09114","article-title":"Genome-wide association study in alopecia areata implicates both innate and adaptive immunity","volume":"466","author":"Petukhova","year":"2010","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2013.01.006","article-title":"Impaired inhibitory function of circulating CD4+CD25+ regulatory T cells in alopecia areata","volume":"70","author":"Shin","year":"2013","journal-title":"J Dermatol Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.immuni.2019.02.013","article-title":"Treg-cell control of a CXCL5-IL-17 inflammatory axis promotes hair-Follicle-Stem-Cell differentiation during skin-barrier repair","volume":"50","author":"Mathur","year":"2019","journal-title":"Immunity"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502139","article-title":"Cutting edge: Regulatory T cells facilitate cutaneous wound healing","volume":"196","author":"Nosbaum","year":"2016","journal-title":"J Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2000372117","article-title":"Proenkephalin(+) regulatory T cells expanded by ultraviolet b exposure maintain skin homeostasis with a healing function","volume":"117","author":"Shime","year":"2020","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.653803","article-title":"Interleukin-33-Dependent accumulation of regulatory T cells mediates pulmonary epithelial regeneration during acute respiratory distress syndrome","volume":"12","author":"Tan","year":"2021","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.immuni.2018.07.011","article-title":"Lung gammadelta T cells mediate protective responses during neonatal influenza infection that are associated with type 2 immunity","volume":"49","author":"Guo","year":"2018","journal-title":"Immunity"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2017-0019OC","article-title":"Foxp3(+) regulatory T cell expression of keratinocyte growth factor enhances lung epithelial proliferation","volume":"57","author":"Dial","year":"2017","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36498","article-title":"CD4+CD25+Foxp3+ tregs resolve experimental lung injury in mice and are present in humans with acute lung injury","volume":"119","author":"D'Alessio","year":"2009","journal-title":"J Clin Invest"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.123919","article-title":"IL-33-mediated IL-13 secretion by ST2+ tregs controls inflammation after lung injury","volume":"4","author":"Liu","year":"2019","journal-title":"JCI Insight"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.33","article-title":"Foxp3+ regulatory T cells promote lung epithelial proliferation","volume":"7","author":"Mock","year":"2014","journal-title":"Mucosal Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1165\/rcmb.2012-0198OC","article-title":"Regulatory T cells reduce acute lung injury fibroproliferation by decreasing fibrocyte recruitment","volume":"48","author":"Garibaldi","year":"2013","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.021","article-title":"A distinct function of regulatory T cells in tissue protection","volume":"162","author":"Arpaia","year":"2015","journal-title":"Cell"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0785-3","article-title":"Interleukin-33 activates regulatory T cells to suppress innate gammadelta T cell responses in the lung","volume":"21","author":"Faustino","year":"2020","journal-title":"Nat Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30348","article-title":"The epidermal growth factor receptor ligand amphiregulin protects from cholestatic liver injury and regulates bile acids synthesis","volume":"69","author":"Santamaria","year":"2019","journal-title":"Hepatology"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00547-x","article-title":"Kidney GATA3(+) regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury","volume":"18","author":"Sakai","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.10.054","article-title":"A special population of regulatory T cells potentiates muscle repair","volume":"155","author":"Burzyn","year":"2013","journal-title":"Cell"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128094","article-title":"FOXP3+ T cells recruited to sites of sterile skeletal muscle injury regulate the fate of satellite cells and guide effective tissue regeneration","volume":"10","author":"Castiglioni","year":"2015","journal-title":"PloS One"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.01.009","article-title":"Poor repair of skeletal muscle in aging mice reflects a defect in local, interleukin-33-Dependent accumulation of regulatory T cells","volume":"44","author":"Kuswanto","year":"2016","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046789","article-title":"A unique population of regulatory T cells in heart potentiates cardiac protection from myocardial infarction","volume":"142","author":"Xia","year":"2020","journal-title":"Circulation"},{"key":"B41","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1161\/CIRCRESAHA.115.303895","article-title":"Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte\/macrophage differentiation","volume":"115","author":"Weirather","year":"2014","journal-title":"Circ Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1927","article-title":"Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke","volume":"15","author":"Liesz","year":"2009","journal-title":"Nat Med"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0824-5","article-title":"Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery","volume":"565","author":"Ito","year":"2019","journal-title":"Nature"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.01.013","article-title":"The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury","volume":"85","author":"Gadani","year":"2015","journal-title":"Neuron"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nm1564","article-title":"Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation","volume":"13","author":"Korn","year":"2007","journal-title":"Nat Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4528","article-title":"Regulatory T cells promote myelin regeneration in the central nervous system","volume":"20","author":"Dombrowski","year":"2017","journal-title":"Nat Neurosci"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201234","article-title":"T Reg cell-intrinsic requirements for ST2 signaling in health and neuroinflammation","volume":"218","author":"Hemmers","year":"2021","journal-title":"J Exp Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.07.019","article-title":"Regulatory T cells promote apelin-mediated sprouting angiogenesis in type 2 diabetes","volume":"24","author":"Leung","year":"2018","journal-title":"Cell Rep"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005407","article-title":"Specialized regulatory T cells control venous blood clot resolution through SPARC","volume":"137","author":"Shahneh","year":"2021","journal-title":"Blood"},{"key":"B50","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41577-018-0083-6","article-title":"Central CD4(+) T cell tolerance: deletion versus regulatory T cell differentiation","volume":"19","author":"Klein","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.11.022","article-title":"Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire","volume":"28","author":"Burchill","year":"2008","journal-title":"Immunity"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.11.021","article-title":"A two-step process for thymic regulatory T cell development","volume":"28","author":"Lio","year":"2008","journal-title":"Immunity"},{"key":"B53","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.immuni.2012.08.023","article-title":"IkappaB(NS) protein mediates regulatory T cell development via induction of the Foxp3 transcription factor","volume":"37","author":"Schuster","year":"2012","journal-title":"Immunity"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.02.022","article-title":"Foxp3 transcription factor is proapoptotic and lethal to developing regulatory T cells unless counterbalanced by cytokine survival signals","volume":"38","author":"Tai","year":"2013","journal-title":"Immunity"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01583","article-title":"Generation of Foxp3(+)CD25(-) regulatory T-cell precursors requires c-rel and IkappaBNS","volume":"10","author":"Schuster","year":"2019","journal-title":"Front Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.965303","article-title":"IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4(+)Foxp3(+) regulatory T lymphocytes","volume":"13","author":"Apert","year":"2022","journal-title":"Front Immunol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/s41590-018-0289-6","article-title":"Thymic regulatory T cells arise via two distinct developmental programs","volume":"20","author":"Owen","year":"2019","journal-title":"Nat Immunol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02382","article-title":"Dynamic imprinting of the treg cell-specific epigenetic signature in developing thymic regulatory T cells","volume":"10","author":"Herppich","year":"2019","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"104026","DOI":"10.1016\/j.cellimm.2019.104026","article-title":"Epigenetic and transcriptional analysis supports human regulatory T cell commitment at the CD4+CD8+ thymocyte stage","volume":"347","author":"Vanhanen","year":"2020","journal-title":"Cell Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151438","article-title":"Control of Foxp3 stability through modulation of TET activity","volume":"213","author":"Yue","year":"2016","journal-title":"J Exp Med"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16221","article-title":"Unique properties of thymic antigen-presenting cells promote epigenetic imprinting of alloantigen-specific regulatory T cells","volume":"8","author":"Garg","year":"2017","journal-title":"Oncotarget"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502352","article-title":"Vitamin c facilitates demethylation of the Foxp3 enhancer in a tet-dependent manner","volume":"196","author":"Sasidharan Nair","year":"2016","journal-title":"J Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.06.110","article-title":"Down-regulation of Tet2 prevents TSDR demethylation in IL2 deficient regulatory T cells","volume":"450","author":"Nair","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"B64","doi-asserted-by":"publisher","first-page":"5368","DOI":"10.1038\/s41467-018-07806-6","article-title":"Interleukin 2 modulates thymic-derived regulatory T cell epigenetic landscape","volume":"9","author":"Chorro","year":"2018","journal-title":"Nat Commun"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3646","article-title":"Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment","volume":"18","author":"Kitagawa","year":"2017","journal-title":"Nat Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3150","article-title":"Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors","volume":"16","author":"Thiault","year":"2015","journal-title":"Nat Immunol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-019-0352-8","article-title":"Recirculating IL-1R2(+) tregs fine-tune intrathymic treg development under inflammatory conditions","volume":"18","author":"Nikolouli","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200089","article-title":"Tracking regulatory T cell development in the thymus using single-cell RNA Sequencing\/TCR sequencing","volume":"209","author":"Owen","year":"2022","journal-title":"J Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031562","article-title":"Developmental stage, phenotype, and migration distinguish naive- and effector\/memory-like CD4+ regulatory T cells","volume":"199","author":"Huehn","year":"2004","journal-title":"J Exp Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636575","article-title":"Induction of organ-selective CD4+ regulatory T cell homing","volume":"37","author":"Siewert","year":"2007","journal-title":"Eur J Immunol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.cell.2018.05.004","article-title":"TCR transgenic mice reveal stepwise, multi-site acquisition of the distinctive fat-treg phenotype","volume":"174","author":"Li","year":"2018","journal-title":"Cell"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2025197118","article-title":"PPARgamma marks splenic precursors of multiple nonlymphoid-tissue treg compartments","volume":"118","author":"Li","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"B73","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.immuni.2019.01.001","article-title":"Single-cell transcriptomics of regulatory T cells reveals trajectories of tissue adaptation","volume":"50","author":"Miragaia","year":"2019","journal-title":"Immunity"},{"key":"B74","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.immuni.2019.12.002","article-title":"Precursors for nonlymphoid-tissue treg cells reside in secondary lymphoid organs and are programmed by the transcription factor BATF","volume":"52","author":"Delacher","year":"2020","journal-title":"Immunity"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat5861","article-title":"Molecular diversification of regulatory T cells in nonlymphoid tissues","volume":"3","author":"DiSpirito","year":"2018","journal-title":"Sci Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3799","article-title":"Genome-wide DNA-methylation landscape defines specialization of regulatory T cells in tissues","volume":"18","author":"Delacher","year":"2017","journal-title":"Nat Immunol"},{"key":"B77","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1038\/s41467-019-09276-w","article-title":"Rbpj expression in regulatory T cells is critical for restraining TH2 responses","volume":"10","author":"Delacher","year":"2019","journal-title":"Nat Commun"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1016\/j.celrep.2019.01.070","article-title":"Blimp1 prevents methylation of Foxp3 and loss of regulatory T cell identity at sites of inflammation","volume":"26","author":"Garg","year":"2019","journal-title":"Cell Rep"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.07.014","article-title":"Epigenetic mechanisms regulating T-cell responses","volume":"142","author":"Schmidl","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737594","article-title":"DNA Demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3(+) conventional T cells","volume":"37","author":"Baron","year":"2007","journal-title":"Eur J Immunol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/j.immuni.2020.04.006","article-title":"Regulatory T cell-specific epigenomic region variants are a key determinant of susceptibility to common autoimmune diseases","volume":"52","author":"Ohkura","year":"2020","journal-title":"Immunity"},{"key":"B82","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.immuni.2021.03.007","article-title":"Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells","volume":"54","author":"Delacher","year":"2021","journal-title":"Immunity"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abk0957","article-title":"BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors","volume":"7","author":"Itahashi","year":"2022","journal-title":"Sci Immunol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2402","article-title":"Transcription factor Foxp3 and its protein partners form a complex regulatory network","volume":"13","author":"Rudra","year":"2012","journal-title":"Nat Immunol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa7017","article-title":"Immune tolerance. regulatory T cells generated early in life play a distinct role in maintaining self-tolerance","volume":"348","author":"Yang","year":"2015","journal-title":"Science"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.991671","article-title":"Inflammatory perturbations in early life long-lastingly shape the transcriptome and TCR repertoire of the first wave of regulatory T cells","volume":"13","author":"Yang","year":"2022","journal-title":"Front Immunol"},{"key":"B87","doi-asserted-by":"publisher","first-page":"9676","DOI":"10.3390\/ijms22189676","article-title":"Regulatory T cell therapy of graft-versus-Host disease: Advances and challenges","volume":"22","author":"Hefazi","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.746889","article-title":"Utilization of treg cells in solid organ transplantation","volume":"13","author":"Juneja","year":"2022","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1082055\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T04:52:58Z","timestamp":1670475178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1082055\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":88,"alternative-id":["10.3389\/fimmu.2022.1082055"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1082055","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,8]]},"article-number":"1082055"}}