The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation. Nat Immunol 2013 Jul;14(7):732-40
Date
06/04/2013Pubmed ID
23727894Pubmed Central ID
PMC4084713DOI
10.1038/ni.2633Scopus ID
2-s2.0-84879355943 (requires institutional sign-in at Scopus site) 114 CitationsAbstract
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.
Author List
Yang XO, Zhang H, Kim BS, Niu X, Peng J, Chen Y, Kerketta R, Lee YH, Chang SH, Corry DB, Wang D, Watowich SS, Dong CAuthor
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAsthma
Cell Differentiation
Histocytochemistry
Immunoblotting
Inflammation
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphorylation
RNA
Real-Time Polymerase Chain Reaction
STAT Transcription Factors
Signal Transduction
Suppressor of Cytokine Signaling Proteins
T-Lymphocytes, Regulatory