{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:32:41Z","timestamp":1787243561276,"version":"build-2736575974"},"reference-count":50,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["mucosalimmunology.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Mucosal Immunology"],"published-print":{"date-parts":[[2023,6]]},"DOI":"10.1016\/j.mucimm.2023.02.007","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T22:00:27Z","timestamp":1679090427000},"page":"264-274","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"title":["Helios+ and ROR\u03b3t+ Treg populations are differentially regulated by MHCII, CD28, and ICOS to shape the intestinal Treg pool"],"prefix":"10.1016","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4902-4372","authenticated-orcid":false,"given":"Elisa","family":"Cruz-Morales","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Hart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia M.","family":"Fossett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9111-4895","authenticated-orcid":false,"given":"Terri M.","family":"Laufer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mucimm.2023.02.007_b0005","doi-asserted-by":"crossref","first-page":"1057","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":"10.1016\/j.mucimm.2023.02.007_b0010","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/s41590-019-0351-z","article-title":"Regulatory T cell adaptation in the intestine and skin","volume":"20","author":"Whibley","year":"2019","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0015","doi-asserted-by":"crossref","first-page":"211","DOI":"10.3389\/fimmu.2012.00211","article-title":"Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome: a paradigm of immunodeficiency with autoimmunity","volume":"3","author":"Barzaghi","year":"2012","journal-title":"Front. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0020","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/mi.2015.74","article-title":"Foxp3+ T cells expressing ROR\u03b3t represent a stable regulatory T-cell effector lineage with enhanced suppressive capacity during intestinal inflammation","volume":"9","author":"Yang","year":"2016","journal-title":"Mucosal Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0025","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41577-021-00519-w","article-title":"Tissue regulatory T cells: regulatory chameleons","volume":"21","author":"Mu\u00f1oz-Rojas","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0030","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1126\/science.aaa9420","article-title":"Individual intestinal symbionts induce a distinct population of ROR\u03b3+ regulatory T cells","volume":"349","author":"Sefik","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.mucimm.2023.02.007_b0035","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1126\/science.aac4263","article-title":"The microbiota regulates type 2 immunity through ROR\u03b3t+ T cells","volume":"349","author":"Ohnmacht","year":"2015","journal-title":"Science"},{"key":"10.1016\/j.mucimm.2023.02.007_b0040","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/nature10772","article-title":"Extrathymically generated regulatory T cells control mucosal Th2 inflammation","volume":"482","author":"Josefowicz","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.mucimm.2023.02.007_b0045","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/nature12079","article-title":"Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota","volume":"497","author":"Cebula","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.mucimm.2023.02.007_b0050","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4049\/jimmunol.1501704","article-title":"Helios controls a limited subset of regulatory T cell functions","volume":"196","author":"Sebastian","year":"2016","journal-title":"J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0055","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/eji.201847935","article-title":"Helios+ and Helios\u2212 Treg subpopulations are phenotypically and functionally distinct and express dissimilar TCR repertoires","volume":"49","author":"Thornton","year":"2019","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0060","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1126\/science.aac5560","article-title":"Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine","volume":"351","author":"Kim","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.mucimm.2023.02.007_b0065","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.4049\/jimmunol.0904028","article-title":"Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells","volume":"184","author":"Thornton","year":"2010","journal-title":"J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0070","doi-asserted-by":"crossref","first-page":"589","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":"10.1016\/j.mucimm.2023.02.007_b0075","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.celrep.2014.11.006","article-title":"Regulatory T cells occupy an isolated niche in the intestine that is antigen independent","volume":"9","author":"Korn","year":"2014","journal-title":"Cell Rep."},{"key":"10.1016\/j.mucimm.2023.02.007_b0080","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1084\/jem.20131142","article-title":"CCR7 provides localized access to IL-2 and defines homeostatically distinct regulatory T cell subsets","volume":"211","author":"Smigiel","year":"2014","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.mucimm.2023.02.007_b0085","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/ni.3004","article-title":"Continuous requirement for the TCR in regulatory T cell function","volume":"15","author":"Levine","year":"2014","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0090","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1600-065X.2009.00775.x","article-title":"Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells","volume":"229","author":"Bour-Jordan","year":"2009","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.mucimm.2023.02.007_b0095","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1002\/eji.201242794","article-title":"ICOS controls Foxp3(+) regulatory T-cell expansion, maintenance and IL-10 production during helminth infection","volume":"43","author":"Redpath","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0100","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.4049\/jimmunol.1601670","article-title":"TCR signaling and CD28\/CTLA-4 signaling cooperatively modulate T regulatory cell homeostasis","volume":"198","author":"Holt","year":"2017","journal-title":"J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0105","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.4049\/jimmunol.1801266","article-title":"Cutting edge: ICOS-deficient regulatory T cells display normal induction of Il10 but readily downregulate expression of Foxp3","volume":"202","author":"Landuyt","year":"2019","journal-title":"J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0110","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.600000","article-title":"CD86 is a selective CD28 ligand supporting FoxP3+ regulatory T cell homeostasis in the presence of high levels of CTLA-4","volume":"11","author":"Halliday","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0115","doi-asserted-by":"crossref","first-page":"851","DOI":"10.4049\/jimmunol.2100653","article-title":"Control of memory phenotype T lymphocyte homeostasis: role of costimulation","volume":"208","author":"Panda","year":"2022","journal-title":"J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0120","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.3389\/fimmu.2019.03100","article-title":"Treg heterogeneity, function, and homeostasis","volume":"10","author":"Shevyrev","year":"2019","journal-title":"Front. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0125","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.4049\/jimmunol.0903740","article-title":"Dendritic cells induce regulatory T cell proliferation through antigen-dependent and -independent interactions","volume":"185","author":"Zou","year":"2010","journal-title":"J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0130","doi-asserted-by":"crossref","first-page":"5078","DOI":"10.4049\/jimmunol.162.9.5078","article-title":"Self-reactive T cells selected on thymic cortical epithelium are polyclonal and are pathogenic in vivo","volume":"162","author":"Laufer","year":"1999","journal-title":"J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0135","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1084\/jem.194.4.427","article-title":"Major histocompatibility complex class II\u2013positive cortical epithelium mediates the selection of CD4(+)25(+) immunoregulatory T cells","volume":"194","author":"Bensinger","year":"2001","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.mucimm.2023.02.007_b0140","doi-asserted-by":"crossref","first-page":"1160","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":"10.1016\/j.mucimm.2023.02.007_b0145","doi-asserted-by":"crossref","first-page":"4503","DOI":"10.1172\/JCI57456","article-title":"GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice","volume":"121","author":"Wohlfert","year":"2011","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.mucimm.2023.02.007_b0150","doi-asserted-by":"crossref","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":"10.1016\/j.mucimm.2023.02.007_b0155","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/ni.2006","article-title":"The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells","volume":"12","author":"Cretney","year":"2011","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0160","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.4049\/jimmunol.160.5.2223","article-title":"CD28 receptor endocytosis is targeted by mutations that disrupt phosphatidylinositol 3-kinase binding and costimulation","volume":"160","author":"C\u00e9fa\u00ef","year":"1998","journal-title":"J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0165","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1073\/pnas.0610543104","article-title":"Interaction of the Wiskott-Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells","volume":"104","author":"Badour","year":"2007","journal-title":"Proc. Natl Acad. Sci. U. S. A."},{"key":"10.1016\/j.mucimm.2023.02.007_b0170","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1084\/jem.20141030","article-title":"Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity","volume":"212","author":"Paterson","year":"2015","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.mucimm.2023.02.007_b0175","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1126\/science.1160062","article-title":"CTLA-4 control over Foxp3+ regulatory T cell function","volume":"322","author":"Wing","year":"2008","journal-title":"Science"},{"key":"10.1016\/j.mucimm.2023.02.007_b0180","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1084\/jem.20110040","article-title":"Sustained antibody responses depend on CD28 function in bone marrow-resident plasma cells","volume":"208","author":"Rozanski","year":"2011","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.mucimm.2023.02.007_b0185","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.107815","article-title":"CD28 regulates metabolic fitness for long-lived plasma cell survival","volume":"31","author":"Utley","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.mucimm.2023.02.007_b0190","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nature12297","article-title":"mTORC1 couples immune signals and metabolic programming to establish T(reg) cell function","volume":"499","author":"Zeng","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.mucimm.2023.02.007_b0195","doi-asserted-by":"crossref","first-page":"481","DOI":"10.4049\/jimmunol.1701477","article-title":"mTOR Complex 1 signaling regulates the generation and function of central and effector FoxP3+ regulatory T cells","volume":"201","author":"Sun","year":"2018","journal-title":"J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0200","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev-immunol-020711-075024","article-title":"Regulation of immune responses by mTOR","volume":"30","author":"Powell","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0205","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.immuni.2014.10.012","article-title":"Continuous T cell receptor signals maintain a functional regulatory T cell pool","volume":"41","author":"Vahl","year":"2014","journal-title":"Immunity"},{"key":"10.1016\/j.mucimm.2023.02.007_b0210","doi-asserted-by":"crossref","first-page":"3348","DOI":"10.4049\/jimmunol.171.7.3348","article-title":"Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells","volume":"171","author":"Tang","year":"2003","journal-title":"J. Immunol."},{"key":"10.1016\/j.mucimm.2023.02.007_b0215","doi-asserted-by":"crossref","first-page":"11790","DOI":"10.1073\/pnas.162359999","article-title":"Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors","volume":"99","author":"Riley","year":"2002","journal-title":"Proc. Natl Acad. Sci. U. S. A."},{"key":"10.1016\/j.mucimm.2023.02.007_b0220","doi-asserted-by":"crossref","first-page":"11796","DOI":"10.1073\/pnas.092284399","article-title":"Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation","volume":"99","author":"Diehn","year":"2002","journal-title":"Proc. Natl Acad. Sci. U. S. A."},{"key":"10.1016\/j.mucimm.2023.02.007_b0225","doi-asserted-by":"crossref","first-page":"6098","DOI":"10.1073\/pnas.0308688101","article-title":"CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-kappaB subunits on IL-8 and Bcl-xL gene promoters","volume":"101","author":"Marinari","year":"2004","journal-title":"Proc. Natl Acad. Sci. U. S. A."},{"key":"10.1016\/j.mucimm.2023.02.007_b0230","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1084\/jem.20160629","article-title":"Class II MHC-independent suppressive adhesion of dendritic cells by regulatory T cells in vivo","volume":"214","author":"Yan","year":"2017","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.mucimm.2023.02.007_b0235","doi-asserted-by":"crossref","first-page":"12835","DOI":"10.1073\/pnas.1406908111","article-title":"Activated group 3 innate lymphoid cells promote T-cell\u2013mediated immune responses","volume":"111","author":"von Burg","year":"2014","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"10.1016\/j.mucimm.2023.02.007_b0240","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s41586-022-05089-y","article-title":"A ROR\u03b3t+ cell instructs gut microbiota-specific Treg cell differentiation","volume":"610","author":"Kedmi","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.mucimm.2023.02.007_b0245","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/s41586-022-05141-x","article-title":"ILC3s select microbiota-specific regulatory T cells to establish tolerance in the gut","volume":"610","author":"Lyu","year":"2022","journal-title":"Nature"},{"key":"10.1016\/j.mucimm.2023.02.007_b0250","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jaut.2010.10.006","article-title":"Limited sufficiency of antigen presentation by dendritic cells in models of central nervous system autoimmunity","volume":"36","author":"Wu","year":"2011","journal-title":"J Autoimmun"}],"container-title":["Mucosal Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S193302192300017X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S193302192300017X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T13:31:45Z","timestamp":1761831105000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S193302192300017X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["S193302192300017X"],"URL":"https:\/\/doi.org\/10.1016\/j.mucimm.2023.02.007","relation":{},"ISSN":["1933-0219"],"issn-type":[{"value":"1933-0219","type":"print"}],"subject":[],"published":{"date-parts":[[2023,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Helios+ and ROR\u03b3t+ Treg populations are differentially regulated by MHCII, CD28, and ICOS to shape the intestinal Treg pool","name":"articletitle","label":"Article Title"},{"value":"Mucosal Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mucimm.2023.02.007","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc. on behalf of Society for Mucosal Immunology.","name":"copyright","label":"Copyright"}]}}