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Adv."],"published-print":{"date-parts":[[2026,8,21]]},"abstract":"<jats:p>\n                    Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T (Treg) cells need to differentiate into effector Treg (eTreg) cells to maintain immune tolerance and tissue homeostasis. While several transcription factors such as Batf and JunB have been reported to be essential for eTreg differentiation and function, the underlying epigenetic mechanism remains unclear. Here, we show that the histone variant H3.3 is enriched in tissue Tregs compared to splenic Tregs and its chaperone Hira is a critical regulator of Treg effector program. Treg specific-deletion of\n                    <jats:italic toggle=\"yes\">Hira<\/jats:italic>\n                    resulted in reduced eTreg population, impaired suppressive function and multi-organ inflammation in mice. Mechanistically, Hira-dependent H3.3 deposition establishes a permissive epigenetic environment by enhancing chromatin accessibility, facilitating H3K36me3 and preventing H3K27me3 modifications on loci of genes enriched for AP-1 family binding motifs and associated with Treg effector function. Furthermore, overexpression of Batf in\n                    <jats:italic toggle=\"yes\">Hira<\/jats:italic>\n                    -deficient Treg cells largely ameliorates their regulatory defects. Together, our findings reveal a previously unreported epigenetic mechanism critical for Treg effector differentiation and function.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeg2679","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:59:26Z","timestamp":1787162366000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["H3.3 chaperone Hira primes the effector program and function of regulatory T cells"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9475-6450","authenticated-orcid":true,"given":"Xiangxiang","family":"Cao","sequence":"first","affiliation":[{"name":"Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China."},{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 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