{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T18:39:43Z","timestamp":1792780783523,"version":"4.5.0"},"reference-count":53,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"43","funder":[{"name":"National Key Research and Development Program of China","award":["NO.2020YFA0804400"],"award-info":[{"award-number":["NO.2020YFA0804400"]}]},{"name":"National Key Research and Development Program of China","award":["NO.2023YFC2308602"],"award-info":[{"award-number":["NO.2023YFC2308602"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,10,23]]},"abstract":"<jats:p>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, as the most important cytolytic cells in adaptive immunity, can differentiate into distinct subpopulations with specific functions and fates. During this process, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells exhibit substantial plasticity in their differentiation trajectory. Notably, epigenetic regulation has emerged as a pivotal mechanism to govern T cell fate decisions. In this study, we demonstrate that the histone methyltransferase NSD2 critically regulates CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation during acute viral infection. While NSD2 deficiency enhances the early expansion of activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, it severely compromises their survival fitness during the contraction phase, leading to a disproportionate collapse of the antigen-specific pool and limiting the establishment of robust long-lived memory. Mechanistically, this defect is driven by the disruption of the H3K36me2-\n                    <jats:italic toggle=\"yes\">Zbtb20<\/jats:italic>\n                    regulatory axis. Furthermore, we show that in the absence of NSD2, CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in tumor exhibit an increased proportion but dysfunctional resident memory T cell phenotype. Collectively, our findings highlight a critical role for NSD2 in providing more mechanistic insights into how epigenetic mechanisms fine-tune T cell differentiation.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee9670","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T17:58:42Z","timestamp":1792778322000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Histone methyltransferase NSD2 shapes CD8\n                    <sup>+<\/sup>\n                    T cell fates through the H3K36me2-\n                    <i>Zbtb20<\/i>\n                    axis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7620-7809","authenticated-orcid":true,"given":"Shijie","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3243-8195","authenticated-orcid":true,"given":"Yifan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huicheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengdi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2824-8151","authenticated-orcid":true,"given":"Xuwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8530-7380","authenticated-orcid":true,"given":"Yuting","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Department of Experiment Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 17165, 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