| First Author | Akitsu A | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7464 | PubMed ID | 26108163 |
| Mgi Jnum | J:223006 | Mgi Id | MGI:5646323 |
| Doi | 10.1038/ncomms8464 | Citation | Akitsu A, et al. (2015) IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2(+)Vgamma6(+)gammadelta T cells. Nat Commun 6:7464 |
| abstractText | Interleukin-17 (IL-17)-producing gammadelta T (gammadelta17) cells have been implicated in inflammatory diseases, but the underlying pathogenic mechanisms remain unclear. Here, we show that both CD4(+) and gammadelta17 cells are required for the development of autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Specifically, activated CD4(+) T cells direct gammadelta T-cell infiltration by inducing CCL2 expression in joints. Furthermore, IL-17 reporter mice reveal that the Vgamma6(+) subset of CCR2(+) gammadelta T cells preferentially produces IL-17 in inflamed joints. Importantly, because IL-1Ra normally suppresses IL-1R expression on gammadelta T cells, IL-1Ra-deficient mice exhibit elevated IL-1R expression on Vgamma6(+) 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. |
