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RNA helicases, including DExD\u2010box helicase 21 (DDX21), are pivotal in RNA metabolism, but their role in T cell\u2010mediated pathology during IBD remains unclear. Here, we demonstrate that\n                    <jats:italic>DDX21<\/jats:italic>\n                    expression in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells correlates with cell cycle and translation pathways in IBD\u2010affected tissues. Conditional deletion of\n                    <jats:italic>Ddx21<\/jats:italic>\n                    in mouse T cells disrupts T cell homeostasis and impairs cell proliferation. Consequently,\n                    <jats:italic>Ddx21<\/jats:italic>\n                    \u2013deficient CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells exhibit resistance to inducing adoptive transfer colitis, with recipients showing reduced T cell infiltration compared to wild\u2010type (WT) counterparts. Mechanistically, DDX21 ensures ribosome biogenesis after T cell activation and facilitates mRNA translation of Transcription factor dp\u20101 (TFDP1), a transcription factor critical for cell cycle progression. Given this dependence on ribosome biogenesis, pharmacological targeting of this pathway via KU55933\u2014an inhibitor of ribosome synthesis\u2010related signaling\u2014recapitulated the protective effects of DDX21 loss: KU55933 alleviated dextran sulfate sodium (DSS)\u2010induced colitis in mice and attenuated pathogenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell expansion. Our findings establish DDX21 as a key regulator of T cell proliferation and highlight its potential as a therapeutic target for IBD and other autoimmune disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.202516653","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:36:13Z","timestamp":1780040173000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RNA Helicase DDX21 Controls CD4\n                    <sup>+<\/sup>\n                    T Cell Proliferation and Promotes Inflammatory Bowel Disease via Translational Control"],"prefix":"10.1002","volume":"13","author":[{"given":"Yujuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Geriatrics Medical Center on Aging of Ruijin Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Center For Immune\u2010Related Diseases At Shanghai Institute of Immunology Ruijin 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