{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:12:44Z","timestamp":1780078364648,"version":"3.54.0"},"reference-count":59,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"22","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81271143, and 82170966"],"award-info":[{"award-number":["81271143, and 82170966"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hubei Provincial Natural Science Foundation of China","award":["2019CFB643"],"award-info":[{"award-number":["2019CFB643"]}]},{"name":"the Intramural Research Program of NIH, NIDCR,"},{"name":"The Intramural Research Program of NIH, NIDCR"},{"name":"The Intramural Research Program of NIH, NIDCR"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,5,29]]},"abstract":"<jats:p>\n                    Human\n                    <jats:italic toggle=\"yes\">FOXP3<\/jats:italic>\n                    shows two isoforms due to exon 2 skipping, and the exon 2 is critical for FOXP3 function in T\n                    <jats:sub>reg<\/jats:sub>\n                    cells. However, the factor(s) regulating its splicing remain unknown. Here, we show that SRSF3 regulates\n                    <jats:italic toggle=\"yes\">FOXP3<\/jats:italic>\n                    exon 2 function and determines T\n                    <jats:sub>reg<\/jats:sub>\n                    cell fate and function in autoimmunity and tumor immunity. Mechanistically, SRSF3 promoted\n                    <jats:italic toggle=\"yes\">FOXP3<\/jats:italic>\n                    exon 2 inclusion and protein expression and thus safeguarded T\n                    <jats:sub>reg<\/jats:sub>\n                    cells, as deletion of\n                    <jats:italic toggle=\"yes\">Srsf3<\/jats:italic>\n                    gene specifically in T\n                    <jats:sub>reg<\/jats:sub>\n                    cells resulted in profound deficiency of T\n                    <jats:sub>reg<\/jats:sub>\n                    cells in mice, leading to lethal systemic inflammation. T\n                    <jats:sub>reg<\/jats:sub>\n                    cells in human tumor showed high SRSF3 expression. SRSF3 was required for human T\n                    <jats:sub>reg<\/jats:sub>\n                    cell\u2013suppressive function. Humanized mice generated with human\n                    <jats:italic toggle=\"yes\">FOXP3<\/jats:italic>\n                    exon 2 and adjacent introns showed significantly reduced tumor formation with the decreased T\n                    <jats:sub>reg<\/jats:sub>\n                    cell function and consequently increased intratumoral CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration. We have thus revealed a previously unrecognized role of SRSF3 in controlling T\n                    <jats:sub>reg<\/jats:sub>\n                    cell fate and function in antitumor immunity and autoimmunity by regulating\n                    <jats:italic toggle=\"yes\">FOXP3<\/jats:italic>\n                    exon 2 inclusion and protein expression.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeh1671","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:00:46Z","timestamp":1780077646000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["SRSF3 determines T\n                    <sub>reg<\/sub>\n                    cell fate in antitumor immunity and autoimmunity"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6960-6199","authenticated-orcid":true,"given":"Rong","family":"Jia","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6713-4439","authenticated-orcid":true,"given":"Jihua","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China."},{"name":"Department of Endodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyan","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1690-3426","authenticated-orcid":true,"given":"Can","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9593-5567","authenticated-orcid":true,"given":"Jun","family":"Jia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shao","sequence":"additional","affiliation":[{"name":"Hubei Cancer Hospital, Wuhan, 430079, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7545-9930","authenticated-orcid":true,"given":"Dunfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9903-1314","authenticated-orcid":true,"given":"Na","family":"Liu","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9335-2114","authenticated-orcid":true,"given":"Wanjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Bethesda, MD, 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