Xiao, XiangBalasubramanian, SavithriLiu, WentaoChu, XiufengWang, HaibinTaparowsky, Elizabeth J.Fu, Yang-XinChoi, YongwonWalsh, Matthew C.Li, Xian Chang2014-03-102012Xiao, Xiang, Savithri Balasubramanian, Wentao Liu, Xiufeng Chu, Haibin Wang, Elizabeth J. Taparowsky, Yang-Xin Fu, Yongwon Choi, Matthew C. Walsh, and Xian Chang Li. 2012. “OX40 signaling favors the induction of TH9 cells and airway inflammation.” Nature immunology 13 (10): 981-990. doi:10.1038/ni.2390. http://dx.doi.org/10.1038/ni.2390.1529-2908http://nrs.harvard.edu/urn-3:HUL.InstRepos:11878907The mechanisms regulating T helper 9 (TH9) cells and TH9-mediated diseases remain poorly defined. Here, we demonstrate that the receptor OX40 (Tnfrsf4) is a powerful inducer of TH9 cells in vitro and TH9-dependent airway inflammation in vivo. Under TGF-β based polarizing conditions, OX40 ligation eliminated production of induced regulatory T cells and TH17 cells, and divertedCD4+Foxp3− T cells to a TH9 phenotype. Mechanistically, OX40 activated the ubiquitin ligase TRAF6, which triggered the induction of NF-kB-inducing kinase (NIK) in CD4+ T cells and the non-canonical NF-kB pathway which subsequently lead toTH9 generation. Thus, our study identifies a previously unknown mechanism of TH9 induction and may have important clinical implications in allergic inflammation.en-USJournal Article2014-03-1010.1038/ni.2390