{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:09:17Z","timestamp":1788804557069,"version":"build-2803163510"},"reference-count":54,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI153174"],"award-info":[{"award-number":["R01AI153174"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:p>Foxp3 deficiency causes a profound loss of immune tolerance, unleashing autoreactive T and B cells, lymphoproliferation, cytokine-driven inflammation, and autoantibody production. This autoimmune pathology is fueled by increased glutamine usage, but it remains unresolved whether glutamine is necessary to produce energy or for intermediate metabolite biosynthesis responsible for immunomodulation. Here, we demonstrate that glutamine utilization for biosynthetic pathways supported autoimmune inflammation in the settings of Foxp3 deficiency and dextran sodium sulfate\u2013induced colitis. By employing a model of autoimmunity driven by Treg-specific loss of Foxp3, we showed that this effect is independent of pathogenic Foxp3-deficient Treg reprogramming. Mechanistically, glutamine biosynthetic pathways sustained conventional T cell activation and proinflammatory cytokine production by preventing inosine accumulation and signaling, thus implicating adenosine pathway modulation in autoreactive T cell dysregulation. Conversely, autoreactive B cell activation and autoantibody production relied on glutamine-dependent asparagine availability, which we identified as a targetable vulnerability for autoantibody formation. These findings highlighted glutamine-driven biosynthetic processes as critical drivers of autoimmunity and revealed distinct metabolic vulnerabilities in autoreactive T and B cells that could be targeted for therapeutic intervention.<\/jats:p>","DOI":"10.1172\/jci.insight.200076","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:01:06Z","timestamp":1788804066000},"source":"Crossref","is-referenced-by-count":0,"title":["Glutamine-dependent biosynthetic pathways fuel autoreactive T and B cells in Foxp3 deficiency\u2013mediated disease"],"prefix":"10.1172","volume":"11","author":[{"given":"Mohammad Adeel","family":"Zafar","sequence":"first","affiliation":[{"name":"Division of Immunology, Boston Children\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Department of Pediatrics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte N.","family":"Hill Machado","sequence":"additional","affiliation":[{"name":"Division of 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