Authors:
Xiang Xiao, Savithri Balasubramanian, Wentao Liu, Xiufeng Chu, Haibin Wang, Elizabeth J Taparowsky, Yang-Xin Fu, Yongwon Choi, Matthew C Walsh, & Xian Chang Li
Summary:
The mechanisms that regulate the TH9 subset of helper T cells and diseases mediated by TH9 cells remain poorly defined. Here we found that the costimulatory receptor OX40 was a powerful inducer of TH9 cells in vitro and TH9 cell–dependent airway inflammation in vivo. In polarizing conditions based on transforming growth factor-β (TGF-β), ligation of OX40 inhibited the production of induced regulatory T cells and the TH17 subset of helper T cells and diverted CD4+Foxp3− T cells to a TH9 phenotype. Mechanistically, OX40 activated the ubiquitin ligase TRAF6, which triggered induction of the kinase NIK in CD4+ T cells and the noncanonical transcription factor NF-κB pathway; this subsequently led to the generation of TH9 cells. Thus, our study identifies a previously unknown mechanism for the induction of TH9 cells and may have important clinical implications in allergic inflammation.
Source:
Nature Immunology; (07/29/12)