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Interleukin-17B Antagonizes Interleukin-25-Mediated Mucosal Inflammation.

Immunity 2015 Apr 21;42(4):692-703
Joseph M. Reynolds1 Young-Hee Lee1 Yun Shi2 Xiaohu Wang3 Pornpimon Angkasekwinai4 Kalyan C. Nallaparaju2 Stephanie Flaherty1 Seon Hee Chang2 Hiroshi Watarai5,6 and Chen Dong3
1. Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA 2. Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, TX 77054, USA 3. Institute for Immunology, Tsinghua University, Beijing 100084, China 4. Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathumthani 12120, Thailand 5. Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan 6. Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan

The interleukin-17 (IL-17) family of cytokines has emerged as a critical player in inflammatory diseases. Among them, IL-25 has been shown to be important in allergic inflammation and protection against parasitic infection. Here we have demonstrated that IL-17B, a poorly understood cytokine, functions to inhibit IL-25-driven inflammation. IL-17B and IL-25, both binding to the interleukin-17 receptor B (IL-17RB), were upregulated in their expression after acute colonic inflammation. Individual inhibition of these cytokines revealed opposing functions in colon inflammation: IL-25 was pathogenic but IL-17B was protective. Similarly opposing phenotypes were observed in Citrobacter rodentium infection and allergic asthma. Moreover, IL-25 was found to promote IL-6 production from colon epithelial cells, which was inhibited by IL-17B. Therefore, our data demonstrate that IL-17B is an anti-inflammatory cytokine in the IL-17 family.