IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2+Vγ6+γδ T cells
書誌事項
- 公開日
- 2015-06-25
- 資源種別
- journal article
- 権利情報
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- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
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- 10.1038/ncomms8464
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title><jats:p>Interleukin-17 (IL-17)-producing γδ T (γδ17) cells have been implicated in inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here, we show that both CD4<jats:sup>+</jats:sup> and γδ17 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 γδ T-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the Vγ6<jats:sup>+</jats:sup> subset of CCR2<jats:sup>+</jats:sup> γδ T cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on γδ T cells, IL-1Ra-deficient mice exhibit elevated IL-1R expression on Vγ6<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>
収録刊行物
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- Nature Communications
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Nature Communications 6 (1), 7464-, 2015-06-25
Springer Science and Business Media LLC
