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

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number7464
JournalNature communications
Volume6
DOIs
Publication statusPublished - 25 Jun 2015

Cite this

Akitsu, A., Ishigame, H., Kakuta, S., Chung, S. H., Ikeda, S., Shimizu, K., Kubo, S., Liu, Y., Umemura, M., Matsuzaki, G., Yoshikai, Y., Saijo, S., & Iwakura, Y. (2015). IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2 + Vγ6 + γδT cells. Nature communications, 6, [7464]. https://doi.org/10.1038/ncomms8464