{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:00:38Z","timestamp":1791644438729,"version":"4.3.4"},"reference-count":68,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,5,6]]},"abstract":"<jats:p>The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-\u03b3\/interleukin (IL)-4 and transforming growth factor (TGF)-\u03b2 activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models of chronic intestinal inflammation by taking advantage of mice that lack T-bet and retroviral transduction techniques, respectively. Whereas retroviral transduction of T-bet in CD62L+ CD4+ T cells exacerbated colitis in reconstituted SCID mice, T-bet\u2013deficient T cells failed to induce colitis in adoptive transfer experiments suggesting that overexpression of T-bet is essential and sufficient to promote Th1-mediated colitis in vivo. Furthermore, T-bet\u2013deficient CD62L\u2212 CD4+ T cells showed enhanced protective functions in Th1-mediated colitis and exhibited increased TGF-\u03b2 signaling suggesting that a T-bet driven pathway of T cell activation controls the intestinal balance between IFN-\u03b3\/IL-4 and TGF-\u03b2 responses and the development of chronic intestinal inflammation in T cell\u2013mediated colitis. Furthermore, TGF-\u03b2 was found to suppress T-bet expression suggesting a reciprocal relationship between TGF-\u03b2 and T-bet in mucosal T cells. In summary, our data suggest a key regulatory role of T-bet in the pathogenesis of T cell\u2013mediated colitis. Specific targeting of this pathway may be a promising novel approach for the treatment of patients with Crohn's disease and other autoimmune diseases mediated by Th1 T lymphocytes.<\/jats:p>","DOI":"10.1084\/jem.20011956","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T12:49:30Z","timestamp":1027687770000},"page":"1129-1143","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":513,"title":["The Transcription Factor T-bet Regulates Mucosal T Cell Activation in Experimental Colitis and Crohn's Disease"],"prefix":"10.1084","volume":"195","author":[{"given":"M.F.","family":"Neurath","sequence":"first","affiliation":[{"name":"1Laboratory of Immunology, I. 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