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

The mechanisms regulating T helper 9 (T(H)9) cells and T(H)9-mediated diseases remain poorly defined. Here, we demonstrate that the receptor OX40 (Tnfrsf4) is a powerful inducer of T(H)9 cells in vitro and T(H)9-dependent airway inflammation in vivo. Under TGF-β based polarizing conditions, OX40 lig...

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Autores principales: Xiao, Xiang, Balasubramanian, Savithri, Liu, Wentao, Chu, Xiufeng, Wang, Haibin, Taparowsky, Elizabeth J., Fu, Yang-Xin, Choi, Yongwon, Walsh, Matthew C., Li, Xian Chang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806044/
https://www.ncbi.nlm.nih.gov/pubmed/22842344
http://dx.doi.org/10.1038/ni.2390
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author Xiao, Xiang
Balasubramanian, Savithri
Liu, Wentao
Chu, Xiufeng
Wang, Haibin
Taparowsky, Elizabeth J.
Fu, Yang-Xin
Choi, Yongwon
Walsh, Matthew C.
Li, Xian Chang
author_facet Xiao, Xiang
Balasubramanian, Savithri
Liu, Wentao
Chu, Xiufeng
Wang, Haibin
Taparowsky, Elizabeth J.
Fu, Yang-Xin
Choi, Yongwon
Walsh, Matthew C.
Li, Xian Chang
author_sort Xiao, Xiang
collection PubMed
description The mechanisms regulating T helper 9 (T(H)9) cells and T(H)9-mediated diseases remain poorly defined. Here, we demonstrate that the receptor OX40 (Tnfrsf4) is a powerful inducer of T(H)9 cells in vitro and T(H)9-dependent airway inflammation in vivo. Under TGF-β based polarizing conditions, OX40 ligation eliminated production of induced regulatory T cells and T(H)17 cells, and divertedCD4(+)Foxp3(−) T cells to a T(H)9 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 toT(H)9 generation. Thus, our study identifies a previously unknown mechanism of T(H)9 induction and may have important clinical implications in allergic inflammation.
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spelling pubmed-38060442013-10-23 OX40 signaling favors the induction of T(H)9 cells and airway inflammation Xiao, Xiang Balasubramanian, Savithri Liu, Wentao Chu, Xiufeng Wang, Haibin Taparowsky, Elizabeth J. Fu, Yang-Xin Choi, Yongwon Walsh, Matthew C. Li, Xian Chang Nat Immunol Article The mechanisms regulating T helper 9 (T(H)9) cells and T(H)9-mediated diseases remain poorly defined. Here, we demonstrate that the receptor OX40 (Tnfrsf4) is a powerful inducer of T(H)9 cells in vitro and T(H)9-dependent airway inflammation in vivo. Under TGF-β based polarizing conditions, OX40 ligation eliminated production of induced regulatory T cells and T(H)17 cells, and divertedCD4(+)Foxp3(−) T cells to a T(H)9 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 toT(H)9 generation. Thus, our study identifies a previously unknown mechanism of T(H)9 induction and may have important clinical implications in allergic inflammation. 2012-07-29 2012-10 /pmc/articles/PMC3806044/ /pubmed/22842344 http://dx.doi.org/10.1038/ni.2390 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Xiao, Xiang
Balasubramanian, Savithri
Liu, Wentao
Chu, Xiufeng
Wang, Haibin
Taparowsky, Elizabeth J.
Fu, Yang-Xin
Choi, Yongwon
Walsh, Matthew C.
Li, Xian Chang
OX40 signaling favors the induction of T(H)9 cells and airway inflammation
title OX40 signaling favors the induction of T(H)9 cells and airway inflammation
title_full OX40 signaling favors the induction of T(H)9 cells and airway inflammation
title_fullStr OX40 signaling favors the induction of T(H)9 cells and airway inflammation
title_full_unstemmed OX40 signaling favors the induction of T(H)9 cells and airway inflammation
title_short OX40 signaling favors the induction of T(H)9 cells and airway inflammation
title_sort ox40 signaling favors the induction of t(h)9 cells and airway inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806044/
https://www.ncbi.nlm.nih.gov/pubmed/22842344
http://dx.doi.org/10.1038/ni.2390
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