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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,16]]},"abstract":"<jats:p>\n                    \u03b3\u03b4 T cells are an abundant T cell population at the mucosa and are important in providing immune surveillance as well as maintaining tissue homeostasis. However, despite \u03b3\u03b4 T cells\u2019 origin in the thymus, detailed mechanisms regulating \u03b3\u03b4 T cell development remain poorly understood.\n                    <jats:italic toggle=\"yes\">N<\/jats:italic>\n                    <jats:sup>6<\/jats:sup>\n                    -methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) represents one of the most common posttranscriptional modifications of messenger RNA (mRNA) in mammalian cells, but whether it plays a role in \u03b3\u03b4 T cell biology is still unclear. Here, we show that depletion of the m\n                    <jats:sup>6<\/jats:sup>\n                    A demethylase ALKBH5 in lymphocytes specifically induces an expansion of \u03b3\u03b4 T cells, which confers enhanced protection against gastrointestinal\n                    <jats:italic toggle=\"yes\">Salmonella typhimurium<\/jats:italic>\n                    infection. Mechanistically, loss of ALKBH5 favors the development of \u03b3\u03b4 T cell precursors by increasing the abundance of m\n                    <jats:sup>6<\/jats:sup>\n                    A RNA modification in thymocytes, which further reduces the expression of several target genes including Notch signaling components\n                    <jats:italic toggle=\"yes\">Jagged1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Notch2<\/jats:italic>\n                    . As a result, impairment of Jagged1\/Notch2 signaling contributes to enhanced proliferation and differentiation of \u03b3\u03b4 T cell precursors, leading to an expanded mature \u03b3\u03b4 T cell repertoire. Taken together, our results indicate a checkpoint role of ALKBH5 and m\n                    <jats:sup>6<\/jats:sup>\n                    A modification in the regulation of \u03b3\u03b4 T cell early development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2203318119","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T15:16:07Z","timestamp":1659971767000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":55,"title":["RNA m\n                    <sup>6<\/sup>\n                    A demethylase ALKBH5 regulates the development of \u03b3\u03b4 T cells"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3236-842X","authenticated-orcid":false,"given":"Chenbo","family":"Ding","sequence":"first","affiliation":[{"name":"Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine","place":["China"]},{"name":"Shanghai Jiao Tong 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Mus musculus (ID 681681). NCBI BioProject. https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/?term=PRJNA681681. Deposited 30 November 2020."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2203318119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T11:38:24Z","timestamp":1746790704000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2203318119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,8]]},"references-count":72,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2022,8,16]]}},"alternative-id":["10.1073\/pnas.2203318119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2203318119","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,8]]},"assertion":[{"value":"2022-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2203318119"}}