Abstract
Transcription factors of the STAT family are critical in the cytokine-mediated functional differentiation of CD4 + helper T cells. Signaling inhibitors of the SOCS family negatively regulate the activation of STAT proteins; however, their roles in the differentiation and function of helper T cells are not well understood. Here we found that the SOCS protein CIS, which was substantially induced by interleukin 4 (IL-4), negatively regulated the activation of STAT3, STAT5 and STAT6 in T cells. CIS-deficient mice spontaneously developed airway inflammation, and CIS deficiency in T cells led to greater susceptibility to experimental allergic asthma. CIS-deficient T cells showed enhanced differentiation into the TH2 and TH9 subsets of helper T cells. STAT5 and STAT6 regulated IL-9 expression by directly binding to the Il9 promoter. Our data thus demonstrate a critical role for CIS in controlling the proallergic generation of helper T cells.
Original language | English (US) |
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Pages (from-to) | 732-740 |
Number of pages | 9 |
Journal | Nature Immunology |
Volume | 14 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2013 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
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