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: Xiang Xiao, Savithri Balasubramanian, Wentao Liu, Xiufeng Chu, Haibin Wang, Elizabeth J Taparowsky, Yang-Xin Fu, Yongwon Choi, Matthew C Walsh, Xian Chang Li
• Journal: Nature immunology (Nat Immunol) Vol. 13 Issue 10 Pg. 981-90 (Oct 2012) ISSN: 1529-2916 [Electronic] United States
• PMID: 22842344 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CD4 Antigens
• Interleukin-9
• NF-kappa B
• OX40 Ligand
• Proto-Oncogene Proteins
• Receptors, OX40
• TNF Receptor-Associated Factor 6
• Trans-Activators
• Transforming Growth Factor beta
• proto-oncogene protein Spi-1
• Protein Serine-Threonine Kinases
• NF-kappa B kinase

Topics

• Animals
• CD4 Antigens (biosynthesis)
• Humans
• Inflammation (immunology, metabolism)
• Interleukin-9 (biosynthesis, metabolism)
• Mice
• NF-kappa B (metabolism)
• OX40 Ligand (immunology, metabolism)
• Protein Serine-Threonine Kinases (biosynthesis, metabolism)
• Proto-Oncogene Proteins (immunology, metabolism)
• Receptors, OX40 (immunology, metabolism)
• Respiratory System (immunology)
• Signal Transduction (immunology)
• T-Lymphocytes, Helper-Inducer (immunology, metabolism)
• TNF Receptor-Associated Factor 6 (biosynthesis, metabolism)
• Trans-Activators (immunology, metabolism)
• Transforming Growth Factor beta (immunology, metabolism)