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Here, we show that both CD4<jats:sup>+<\/jats:sup> and \u03b3\u03b417 cells are required for the development of autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4<jats:sup>+<\/jats:sup> T cells direct \u03b3\u03b4 T-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the V\u03b36<jats:sup>+<\/jats:sup> subset of CCR2<jats:sup>+<\/jats:sup> \u03b3\u03b4 T cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on \u03b3\u03b4 T cells, IL-1Ra-deficient mice exhibit elevated IL-1R expression on V\u03b36<jats:sup>+<\/jats:sup> cells, which play a critical role in inducing them to produce IL-17. Our findings demonstrate a pathogenic mechanism in which adaptive and innate immunity induce an autoimmune disease in a coordinated manner.<\/jats:p>","DOI":"10.1038\/ncomms8464","type":"journal-article","created":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T10:37:58Z","timestamp":1435228678000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":125,"title":["IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2+V\u03b36+\u03b3\u03b4 T cells"],"prefix":"10.1038","volume":"6","author":[{"given":"Aoi","family":"Akitsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harumichi","family":"Ishigame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Kakuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-hyun","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Umemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goro","family":"Matsuzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunobu","family":"Yoshikai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinobu","family":"Saijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,6,25]]},"reference":[{"key":"BFncomms8464_CR1","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.immuni.2011.02.012","volume":"34","author":"Y Iwakura","year":"2011","unstructured":"Iwakura, Y., Ishigame, H., Saijo, S. & Nakae, S. 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