IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2 + Vγ6 + γδT cells

Aoi Akitsu, Harumichi Ishigame, Shigeru Kakuta, Soo Hyun Chung, Satoshi Ikeda, Kenji Shimizu, Sachiko Kubo, Yang Liu, Masayuki Umemura, Goro Matsuzaki, Yasunobu Yoshikai, Shinobu Saijo, Yoichiro Iwakura

    研究成果: Contribution to journalArticle査読

    62 被引用数 (Scopus)

    抄録

    Interleukin-17 (IL-17)-producing γδT (γδ17) cells have been implicated in inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here, we show that both CD4 + and γδ17 cells are required for the development of autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4 + T cells direct γδT-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the Vγ6 + subset of CCR2 + γδT cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on γδT cells, IL-1Ra-deficient mice exhibit elevated IL-1R expression on Vγ6 + 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.

    本文言語英語
    論文番号7464
    ジャーナルNature communications
    6
    DOI
    出版ステータス出版済み - 6 25 2015

    All Science Journal Classification (ASJC) codes

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

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