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Publication : OX40 signaling favors the induction of T(H)9 cells and airway inflammation.

First Author  Xiao X Year  2012
Journal  Nat Immunol Volume  13
Issue  10 Pages  981-90
PubMed ID  22842344 Mgi Jnum  J:187731
Mgi Id  MGI:5437832 Doi  10.1038/ni.2390
Citation  Xiao X, et al. (2012) OX40 signaling favors the induction of T(H)9 cells and airway inflammation. Nat Immunol 13(10):981-90
abstractText  The mechanisms that regulate the T(H)9 subset of helper T cells and diseases mediated by T(H)9 cells remain poorly defined. Here we found that the costimulatory receptor OX40 was a powerful inducer of T(H)9 cells in vitro and T(H)9 cell-dependent airway inflammation in vivo. In polarizing conditions based on transforming growth factor-beta (TGF-beta), ligation of OX40 inhibited the production of induced regulatory T cells and the T(H)17 subset of helper T cells and diverted CD4(+)Foxp3(-) T cells to a T(H)9 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-kappaB pathway; this subsequently led to the generation of T(H)9 cells. Thus, our study identifies a previously unknown mechanism for the induction of T(H)9 cells and may have important clinical implications in allergic inflammation.
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