Publication: OX40 signaling favors the induction of TH9 cells and airway inflammation
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2012
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Xiao, 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.
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Abstract
The 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.
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