{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T13:35:31Z","timestamp":1780666531792,"version":"3.54.1"},"reference-count":64,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,8,7]]},"abstract":"<jats:p>Experimental autoimmune myocarditis (EAM) appears after infectious heart disease, the most common cause of dilated cardiomyopathy in humans. Here we report that mice lacking T-bet, a T-box transcription factor required for T helper (Th)1 cell differentiation and interferon (IFN)-\u03b3 production, develop severe autoimmune heart disease compared to T-bet\u2212\/\u2212 control mice. Experiments in T-bet\u2212\/\u2212 IL-4\u2212\/\u2212 and T-bet\u2212\/\u2212 IL-4R\u03b1\u2212\/\u2212 mice, as well as transfer of heart-specific Th1 and Th2 cell lines, showed that autoimmune heart disease develops independently of Th1 or Th2 polarization. Analysis of T-bet\u2212\/\u2212 IL-12R\u03b21\u2212\/\u2212 and T-bet\u2212\/\u2212 IL-12p35\u2212\/\u2212 mice then identified interleukin (IL)-23 as critical for EAM pathogenesis. In addition, T-bet\u2212\/\u2212 mice showed a marked increase in production of the IL-23\u2013dependent cytokine IL-17 by heart-infiltrating lymphocytes, and in vivo IL-17 depletion markedly reduced EAM severity in T-bet\u2212\/\u2212 mice. Heart-infiltrating T-bet\u2212\/\u2212 CD8+ but not CD8\u2212 T cells secrete IFN-\u03b3, which inhibits IL-17 production and protects against severe EAM. In contrast, T-bet\u2212\/\u2212 CD8+ lymphocytes completely lost their capacity to release IFN-\u03b3 within the heart. Collectively, these data show that severe IL-17\u2013mediated EAM can develop in the absence of T-bet, and that T-bet can regulate autoimmunity via the control of nonspecific CD8+ T cell bystander functions in the inflamed target organ.<\/jats:p>","DOI":"10.1084\/jem.20052222","type":"journal-article","created":{"date-parts":[[2006,8,2]],"date-time":"2006-08-02T03:47:53Z","timestamp":1154490473000},"page":"2009-2019","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":215,"title":["T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17"],"prefix":"10.1084","volume":"203","author":[{"given":"Manu","family":"Rangachari","sequence":"first","affiliation":[{"name":"1Institute for Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria"},{"name":"2Graduate Programme in Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Mauermann","sequence":"additional","affiliation":[{"name":"3Department of Research and Department of Internal Medicine, Experimental Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene\u0301 R.","family":"Marty","sequence":"additional","affiliation":[{"name":"3Department of Research and Department of Internal Medicine, Experimental Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Dirnhofer","sequence":"additional","affiliation":[{"name":"4Department of Pathology, University Hospital, CH-4031 Basel, Switzerl"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael O.","family":"Kurrer","sequence":"additional","affiliation":[{"name":"5Department of Pathology, University Hospital, CH-8091 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vukoslav","family":"Komnenovic","sequence":"additional","affiliation":[{"name":"1Institute for Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef M.","family":"Penninger","sequence":"additional","affiliation":[{"name":"1Institute for Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urs","family":"Eriksson","sequence":"additional","affiliation":[{"name":"3Department of Research and Department of Internal Medicine, Experimental Critical Care Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2006,7,31]]},"reference":[{"key":"2023072515165099000_BIB1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.biocel.2004.06.014","volume":"37","year":"2005","journal-title":"Int. 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