@article{09581944aac946ec85203115da0b0696,
title = "IL-1 receptor antagonist-deficient mice develop autoimmune arthritis due to intrinsic activation of IL-17-producing CCR2 + Vγ6 + γδT cells",
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.",
author = "Aoi Akitsu and Harumichi Ishigame and Shigeru Kakuta and Chung, {Soo Hyun} and Satoshi Ikeda and Kenji Shimizu and Sachiko Kubo and Yang Liu and Masayuki Umemura and Goro Matsuzaki and Yasunobu Yoshikai and Shinobu Saijo and Yoichiro Iwakura",
note = "Funding Information: We thank S. Fujii (RIKEN, Kanagawa, Japan) for providing us with Cd4−/− mice. Y. Ishii and A. Fujita (FACS Core Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan) for cell sorting; H. Saito (The University of Tokyo) for studentship support; K. Shibata (Kyushu University, Fukuoka, Japan) for reading the manuscript and for valuable discussion; A. Seno for technical assistance in designing the figures; and all members of our laboratory for excellent animal care. This work was supported by CREST (Y.I.), Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Y.I.), the Scientific Technique Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry (Y.I.) and the JSPS (A.A.). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",
year = "2015",
month = jun,
day = "25",
doi = "10.1038/ncomms8464",
language = "English",
volume = "6",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}