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Our previous study using T-bet transgenic mice revealed over-expression of T-bet completely suppressed collagen-induced arthritis (CIA), a murine model of RA, indicating a potential suppressive role of T-bet in the pathogenesis of autoimmune arthritis. Here, we show T-bet-deficiency exacerbated CIA. T-bet in CD4\u2009+\u2009T cells, but not in CD11c\u2009+\u2009dendritic cells, was critical for regulating the production of IL-17A, IL-17F, IL-22, and TNF\u03b1 from CD4\u2009+\u2009T cells. T-bet-deficient CD4\u2009+\u2009T cells showed higher ROR\u03b3t expression and increased IL-17A production in ROR\u03b3t-positive cells after CII immunization. In addition, T-bet-deficient na\u00efve CD4\u2009+\u2009T cells showed accelerated Th17 differentiation in vitro. CIA induced in CD4-Cre T-bet<jats:sup>fl\/fl<\/jats:sup> (cKO) mice was more severe and T-bet-deficient CD4\u2009+\u2009T cells in the arthritic joints of cKO mice showed higher ROR\u03b3t expression and increased IL-17A production. Transcriptome analysis of T-bet-deficient CD4\u2009+\u2009T cells revealed that expression levels of Th17-related genes were selectively increased. Our results indicate that T-bet in CD4\u2009+\u2009T cells repressed ROR\u03b3t expression and function resulting in suppression of arthritogenic Th17 cells and CIA.<\/jats:p>","DOI":"10.1038\/s41598-021-96699-5","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T10:02:57Z","timestamp":1630317777000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through inhibition of ROR\u03b3t expression and function"],"prefix":"10.1038","volume":"11","author":[{"given":"Masaru","family":"Shimizu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reona","family":"Tanimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotona","family":"Furuyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yokosawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromitsu","family":"Asashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Tsuboi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Sumida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"96699_CR1","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/S0092-8674(00)80702-3","volume":"100","author":"SJ Szabo","year":"2000","unstructured":"Szabo, S. 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