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Immunol."],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>\n                    Regulatory T cells (T\n                    <jats:sub>reg<\/jats:sub>\n                    cells) express the master regulator, Foxp3, and display distinctive epigenetic landscapes ensuring T\n                    <jats:sub>reg<\/jats:sub>\n                    cell\u2013specific gene expression and stable suppressive functions, yet Foxp3\u2019s contribution to this epigenetic identity remains unclear. Leveraging Foxp3-transduced conventional T cells as a gain-of-function probe in mice, we identified a previously unrecognized subset that acquires endogenous\n                    <jats:italic toggle=\"yes\">Foxp3<\/jats:italic>\n                    expression, T\n                    <jats:sub>reg<\/jats:sub>\n                    cell\u2013like transcriptomic and chromatin features, and suppressive functions exclusively in vivo. These Foxp3-driven features were conserved in T\n                    <jats:sub>reg<\/jats:sub>\n                    cells but impaired in Foxp3-mutant T\n                    <jats:sub>reg<\/jats:sub>\n                    -like cells, demonstrating a Foxp3 requirement. Induction of endogenous\n                    <jats:italic toggle=\"yes\">Foxp3<\/jats:italic>\n                    expression in vivo required reduced AKT-mTOR signaling and Foxp3-dependent engagement of STAT5 and nuclear factor \u03baB (NF-\u03baB). Temporal chromatin profiling revealed stepwise Foxp3-driven regulatory programs, including a core program shared across T\n                    <jats:sub>reg<\/jats:sub>\n                    cell subsets and effector-specific programs, both associated with NF-\u03baB activity and Foxp3 binding. Thus, Foxp3 integrates cell-intrinsic and environmental contexts to drive epigenetic programs defining T\n                    <jats:sub>reg<\/jats:sub>\n                    cell identities and functions, with implications for Foxp3-based therapies.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.aed2111","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T17:58:16Z","timestamp":1777658296000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Foxp3 drives context-dependent epigenetic programs that define regulatory T cell molecular identity and function"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6162-962X","authenticated-orcid":true,"given":"Yuxi","family":"Wei","sequence":"first","affiliation":[{"name":"Laboratory of Immunology and Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinako","family":"Ago","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8257-585X","authenticated-orcid":true,"given":"Ryuichi","family":"Murakami","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan."},{"name":"Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Funatsu","sequence":"additional","affiliation":[{"name":"Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences, Yokohama, 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Experimental Pathology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-6094","authenticated-orcid":true,"given":"Shimon","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan."},{"name":"Laboratory of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8770-4593","authenticated-orcid":true,"given":"Shohei","family":"Hori","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan."},{"name":"Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences, 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Hori Foxp3 drives context-dependent epigenetic programs that define regulatory T cell molecular identity and function (Zenodo 2026); https:\/\/doi.org\/10.5281\/zenodo.18452444."},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr064"}],"container-title":["Science Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.aed2111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T17:58:19Z","timestamp":1777658299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.aed2111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":81,"journal-issue":{"issue":"119","published-print":{"date-parts":[[2026,5,1]]}},"alternative-id":["10.1126\/sciimmunol.aed2111"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.aed2111","relation":{},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]},"assertion":[{"value":"2025-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaed2111"}}