title: OX40 signaling favors the induction of T(H)9 cells and airway inflammation.
abstract: 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-β (TGF-β), 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-κB 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.
authors: Transplant Research Center, Brigham and Women's Hospital and Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
authors: Xiang
authors: X
authors: Xiao
authors: Savithri
authors: S
authors: Balasubramanian
authors: Wentao
authors: W
authors: Liu
authors: Xiufeng
authors: X
authors: Chu
authors: Haibin
authors: H
authors: Wang
authors: Elizabeth J
authors: EJ
authors: Taparowsky
authors: Yang-Xin
authors: YX
authors: Fu
authors: Yongwon
authors: Y
authors: Choi
authors: Matthew C
authors: MC
authors: Walsh
authors: Xian Chang
authors: XC
authors: Li
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016906:Interleukin-9 / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D053278:OX40 Ligand / Q000276:immunology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism; D053262:Receptors, OX40 / Q000276:immunology / Q000378:metabolism*; D012137:Respiratory System / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000096:biosynthesis / Q000378:metabolism; D015534:Trans-Activators / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D015704:CD4 Antigens; D016906:Interleukin-9; D016328:NF-kappa B; D053278:OX40 Ligand; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D053262:Receptors, OX40; D048029:TNF Receptor-Associated Factor 6; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D000097782:NF-kappaB-Inducing Kinase; D000099232:Proto-Oncogene Protein Spi-1