研究成果・発表論文

IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2$^+$V\ensuremathγ6$^+$\ensuremathγ\ensuremathδ T cells

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


要旨
Interleukin-17 (IL-17)-producing \ensuremathγ\ensuremathδ T (\ensuremathγ\ensuremathδ17) cells have been implicated in inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here, we show that both CD4$^+$ and \ensuremathγ\ensuremathδ17 cells are required for the development of autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4$^+$ T cells direct \ensuremathγ\ensuremathδ T-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the V\ensuremathγ6$^+$ subset of CCR2$^+$ \ensuremathγ\ensuremathδ T cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on \ensuremathγ\ensuremathδ T cells, IL-1Ra- deficient mice exhibit elevated IL-1R expression on V\ensuremathγ6$^+$ 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.






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