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OX40 signaling favors the induction of TH9 cells and airway inflammation
Open accessAbstract
The mechanisms that regulate the TH9 subset of helper T cells and diseases mediated by TH9 cells remain poorly defined. Here we found that the costimulatory receptor OX40 was a powerful inducer of TH9 cells in vitro and TH9 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 TH17 subset of helper T cells and diverted CD4+Foxp3− T cells to a TH9 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 TH9 cells. Thus, our study identifies a previously unknown mechanism for the induction of TH9 cells and may have important clinical implications in allergic inflammation.
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Mast cells are essential intermediaries in regulatory T-cell tolerance
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Cited by
Molecular mechanisms of T cell co-stimulation and co-inhibition
Chen, L., & Flies, D. B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3405 · Cited by 3,114
The non-canonical NF-κB pathway in immunity and inflammation
Sun, S.-C. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2017.52 · Cited by 1,891
Lambrecht, B. N., & Hammad, H. (2015) · Nature Immunology · doi:10.1038/ni.3049 · Cited by 1,673
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Regulation of the Immune Response by TGF-β: From Conception to Autoimmunity and Infection
Sanjabi, S., Oh, S. A., & Li, M. O. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022236 · Cited by 621
Metadata
- Authors
- Xiao, X., Balasubramanian, S., Liu, W., Chu, X., Wang, H., Taparowsky, E. J., Fu, Y.-X., Choi, Y., Walsh, M. C., & Li, X. C.
- Venue
- Nature Immunology
- Published
- 2012-07-29
- Volume
- 13
- Issue
- 10
- Pages
- 981-990
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2079257757
- Cited by
- 237
- References
- 7
- FWCI
- 6.66
- Type
- journal article
- Language
- en
- Open access
- green
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- Xiao, X., Balasubramanian, S., Liu, W., Chu, X., Wang, H., Taparowsky, E. J., Fu, Y.-X., Choi, Y., Walsh, M. C., & Li, X. C. (2012). OX40 signaling favors the induction of TH9 cells and airway inflammation. Nature Immunology. https://doi.org/10.1038/ni.2390
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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