Abstract
The physiological regulation of the expression of interleukin (IL)-9, a cytokine traditionally regarded as being TH2 associated, remains unclear. Here, we show that IL-9-expressing T cells generated in vitro in the presence of transforming growth factor-β and IL-4 express high levels of mRNA for IL-17 receptor B (IL-17RB), the receptor for IL-25. Treatment of these cells with IL-25 enhances IL-9 expression in vitro. Moreover, transgenic and retroviral overexpression of IL-17RB in T cells results in IL-25-induced IL-9 production that is IL-4 independent. In vivo, the IL-25–IL-17RB pathway regulates IL-9 expression in allergic airway inflammation. Thus, IL-25 is a newly identified regulator of IL-9 expression.
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Acknowledgements
We thank S. Rivera, S.J. Kuschert and J. Parker-Thornburg for their help in generation of knockout and transgenic animals, D. Littman (New York University School of Medicine) for the CD4 mini-gene plasmid, K. Murphy for GFP-RV vector, Amgen for IL-17-receptor deficient mice, J. van Snick for an anti–IL-9 staining antibody, B. Stockinger and M. Veldhoen for suggestions and the Dong lab members for their help and discussion. The work is supported by research grants from NIH (to C.D.). P.A. receives a fellowship from Royal Thai government and C.D. is a Trust Fellow of the MD Anderson Cancer Center and a Leukemia and Lymphoma Society Scholar.
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P.A. and C.D. designed the research and analyzed and interpreted the results, P.A., S.H.C. and M.T. did the experiments, H.W. generated and labeled anti-IL-17RB antibody for staining and P.A. and C.D. prepared the manuscript.
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Angkasekwinai, P., Chang, S., Thapa, M. et al. Regulation of IL-9 expression by IL-25 signaling. Nat Immunol 11, 250–256 (2010). https://doi.org/10.1038/ni.1846
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DOI: https://doi.org/10.1038/ni.1846
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