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One of these genes codes for the RNA helicase DExD\/H-Box Polypeptide 39B (DDX39B), which shows genetic and functional epistasis with interleukin-7 receptor-\u03b1 gene (\n                    <jats:italic>IL7R<\/jats:italic>\n                    ) in MS-risk. Based on evolutionary and functional arguments, we postulated that DDX39B enhances immune tolerance thereby decreasing MS risk. Consistent with such a role we show that DDX39B controls the expression of many MS susceptibility genes and important immune-related genes. Among these we identified\n                    <jats:italic>Forkhead Box P3<\/jats:italic>\n                    (\n                    <jats:italic>FOXP3<\/jats:italic>\n                    ), which codes for the master transcriptional factor in CD4\n                    <jats:sup>+<\/jats:sup>\n                    \/CD25\n                    <jats:sup>+<\/jats:sup>\n                    T regulatory cells. DDX39B knockdown led to loss of immune-regulatory and gain of immune-effector expression signatures. Splicing of\n                    <jats:italic>FOXP3<\/jats:italic>\n                    introns, which belong to a previously unrecognized type of introns with C-rich polypyrimidine tracts, was exquisitely sensitive to DDX39B levels. Given the importance of FOXP3 in autoimmunity, this work cements DDX39B as an important guardian of immune tolerance.\n                  <\/jats:p>","DOI":"10.7554\/elife.76927","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T12:19:33Z","timestamp":1683634773000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.76927","source":"Crossref","is-referenced-by-count":23,"title":["The RNA helicase DDX39B activates FOXP3 RNA splicing to control T regulatory cell fate"],"prefix":"10.7554","volume":"12","author":[{"given":"Minato","family":"Hirano","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/016tfm930","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, University of Texas Medical Branch","place":["Galveston, United States"]},{"id":[{"id":"https:\/\/ror.org\/03ppx1p25","id-type":"ROR","asserted-by":"publisher"}],"name":"National Research Center for the Control and Prevention of 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