{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:48:16Z","timestamp":1787168896424,"version":"build-2736575974"},"reference-count":42,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H06295"],"award-info":[{"award-number":["16H06295"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K15491"],"award-info":[{"award-number":["22K15491"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003382","name":"Core Research for Evolutional Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003382","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Reports"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.celrep.2025.115791","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T11:47:17Z","timestamp":1749210437000},"page":"115791","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Thymically imprinted heterogeneity results in differential Treg induction and stability of effector identity"],"prefix":"10.1016","volume":"44","author":[{"given":"Nathan D.","family":"Pennock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamin","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumi","family":"Ishihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamami","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Cross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimon","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5281-0799","authenticated-orcid":false,"given":"Jason T.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.celrep.2025.115791_bib1","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/nri2416","article-title":"Lineage fate and intense debate: myths, models and mechanisms of CD4- versus CD8-lineage choice","volume":"8","author":"Singer","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0092-8674(94)90169-4","article-title":"T cell receptor antagonist peptides induce positive selection","volume":"76","author":"Hogquist","year":"1994","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.115791_bib3","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/46218","article-title":"Selecting and maintaining a diverse T-cell repertoire","volume":"402","author":"Goldrath","year":"1999","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.115791_bib4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1152\/advan.00066.2013","article-title":"T cell responses: na\u00efve to memory and everything in between","volume":"37","author":"Pennock","year":"2013","journal-title":"Adv. Physiol. Educ."},{"key":"10.1016\/j.celrep.2025.115791_bib5","doi-asserted-by":"crossref","first-page":"40","DOI":"10.4049\/jimmunol.172.1.40","article-title":"A Role for TCR Affinity in Regulating Naive T Cell Homeostasis","volume":"172","author":"Kieper","year":"2004","journal-title":"J. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib6","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/ni.2822","article-title":"Intrinsic CD4+ T cell sensitivity and response to a pathogen are set and sustained by avidity for thymic and peripheral complexes of self peptide and MHC","volume":"15","author":"Persaud","year":"2014","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib7","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms11291","article-title":"Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner","volume":"7","author":"White","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2025.115791_bib8","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/ni.3043","article-title":"The TCR's sensitivity to self peptide-MHC dictates the ability of naive CD8(+) T cells to respond to foreign antigens","volume":"16","author":"Fulton","year":"2015","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib9","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1084\/jem.188.12.2301","article-title":"CD5 Expression Is Developmentally Regulated By T Cell Receptor (TCR) Signals and TCR Avidity","volume":"188","author":"Azzam","year":"1998","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.celrep.2025.115791_bib10","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1126\/science.7542801","article-title":"A role for CD5 in TCR-mediated signal transduction and thymocyte selection","volume":"269","author":"Tarakhovsky","year":"1995","journal-title":"Science"},{"key":"10.1016\/j.celrep.2025.115791_bib11","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/JLB.MR0618-226R","article-title":"The multiple faces of CD5","volume":"105","author":"Burgueno-Bucio","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.celrep.2025.115791_bib12","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/86302","article-title":"Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide","volume":"2","author":"Jordan","year":"2001","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib13","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.immuni.2016.04.018","article-title":"Thymus-Derived Regulatory T Cells Are Positively Selected on Natural Self-Antigen through Cognate Interactions of High Functional Avidity","volume":"44","author":"Kieback","year":"2016","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2025.115791_bib14","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.immuni.2015.02.010","article-title":"CD5 instructs extrathymic regulatory T cell development in response to self and tolerizing antigens","volume":"42","author":"Henderson","year":"2015","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2025.115791_bib15","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1038\/ncomms3209","article-title":"Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells","volume":"4","author":"Martin","year":"2013","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2025.115791_bib16","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/ni1428","article-title":"Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice","volume":"8","author":"Kim","year":"2007","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib17","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1073\/pnas.0811556106","article-title":"Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity","volume":"106","author":"Komatsu","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2025.115791_bib18","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.4049\/jimmunol.1501050","article-title":"T Cell Adolescence: Maturation Events Beyond Positive Selection","volume":"195","author":"Hogquist","year":"2015","journal-title":"J. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib19","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S1074-7613(00)80282-4","article-title":"Identification of a naturally occurring ligand for thymic positive selection","volume":"6","author":"Hogquist","year":"1997","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2025.115791_bib20","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1084\/jem.20110308","article-title":"T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse","volume":"208","author":"Moran","year":"2011","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.celrep.2025.115791_bib21","doi-asserted-by":"crossref","first-page":"12258","DOI":"10.1073\/pnas.1922600117","article-title":"Epigenetic conversion of conventional T cells into regulatory T cells by CD28 signal deprivation","volume":"117","author":"Mikami","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2025.115791_bib22","doi-asserted-by":"crossref","DOI":"10.1038\/s41586-025-09356-6","article-title":"Genome-wide CRISPR screen in human T cells reveals regulators of FOXP3","author":"Chen","year":"2025","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.115791_bib23","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0250533","article-title":"Macrophage and dendritic cell subset composition can distinguish endotypes in adjuvant-induced asthma mouse models","volume":"16","author":"Ozkan","year":"2021","journal-title":"PLoS One"},{"key":"10.1016\/j.celrep.2025.115791_bib24","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1084\/jem.20121849","article-title":"Lung-resident tissue macrophages generate Foxp3+ regulatory T cells and promote airway tolerance","volume":"210","author":"Soroosh","year":"2013","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.celrep.2025.115791_bib25","article-title":"Regulatory T Cells, a Viable Target Against Airway Allergic Inflammatory Responses in Asthma","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.immuni.2014.06.013","article-title":"Origin and functions of tissue macrophages","volume":"41","author":"Epelman","year":"2014","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2025.115791_bib27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/imr.12220","article-title":"Mononuclear phagocytes of the intestine, the skin, and the lung","volume":"262","author":"Scott","year":"2014","journal-title":"Immunol. Rev."},{"key":"10.1016\/j.celrep.2025.115791_bib28","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2025.115791_bib29","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.immuni.2007.04.017","article-title":"Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor","volume":"27","author":"Yamaguchi","year":"2007","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2025.115791_bib30","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/ni.2928","article-title":"Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease","volume":"15","author":"Miyazaki","year":"2014","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib31","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1177\/0022034518759302","article-title":"RANKL Triggers Treg-Mediated Immunoregulation in Inflammatory Osteolysis","volume":"97","author":"Francisconi","year":"2018","journal-title":"J. Dent. Res."},{"key":"10.1016\/j.celrep.2025.115791_bib32","article-title":"Zinc finger protein Zfp335 controls early T-cell development and survival through \u03b2-selection-dependent and -independent mechanisms","volume":"11","author":"Wang","year":"2022","journal-title":"eLife"},{"key":"10.1016\/j.celrep.2025.115791_bib33","doi-asserted-by":"crossref","first-page":"6329","DOI":"10.4049\/jimmunol.1100061","article-title":"IL-2 controls the stability of Foxp3 expression in TGF-beta-induced Foxp3+ T cells in vivo","volume":"186","author":"Chen","year":"2011","journal-title":"J. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib34","doi-asserted-by":"crossref","first-page":"280","DOI":"10.4049\/jimmunol.178.1.280","article-title":"IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells","volume":"178","author":"Burchill","year":"2007","journal-title":"J. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib35","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.immuni.2009.11.014","article-title":"T cell receptor-dependent regulation of lipid rafts controls naive CD8+ T cell homeostasis","volume":"32","author":"Cho","year":"2010","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2025.115791_bib36","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41422-020-0324-7","article-title":"Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases","volume":"30","author":"Ohkura","year":"2020","journal-title":"Cell Res."},{"key":"10.1016\/j.celrep.2025.115791_bib37","doi-asserted-by":"crossref","DOI":"10.1126\/science.abg2752","article-title":"CD5 expression by dendritic cells directs T cell immunity and sustains immunotherapy responses","volume":"379","author":"He","year":"2023","journal-title":"Science"},{"key":"10.1016\/j.celrep.2025.115791_bib38","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3389\/fimmu.2015.00621","article-title":"Functional Heterogeneity in CD4(+) T Cell Responses Against a Bacterial Pathogen","volume":"6","author":"Milam","year":"2015","journal-title":"Front. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib39","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1002\/eji.202048788","article-title":"CD5 levels define functionally heterogeneous populations of na\u00efve human CD4+ T cells","volume":"51","author":"Sood","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.celrep.2025.115791_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.110064","article-title":"Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential","volume":"37","author":"Rogers","year":"2021","journal-title":"Cell Rep."},{"key":"10.1016\/j.celrep.2025.115791_bib41","doi-asserted-by":"crossref","first-page":"14342","DOI":"10.1073\/pnas.1922525117","article-title":"CD5 dynamically calibrates basal NF-\u03baB signaling in T cells during thymic development and peripheral activation","volume":"117","author":"Matson","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2025.115791_bib42","article-title":"Protocol to evaluate cell lineage stability of mouse natural and induced regulatory T cells using bisulfite sequencing","volume":"3","author":"Arai","year":"2022","journal-title":"STAR Protoc."}],"container-title":["Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124725005625?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124725005625?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T11:56:40Z","timestamp":1762603000000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211124725005625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":42,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["S2211124725005625"],"URL":"https:\/\/doi.org\/10.1016\/j.celrep.2025.115791","relation":{},"ISSN":["2211-1247"],"issn-type":[{"value":"2211-1247","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Thymically imprinted heterogeneity results in differential Treg induction and stability of effector identity","name":"articletitle","label":"Article Title"},{"value":"Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.celrep.2025.115791","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"115791"}}