title: The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation.
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.
authors.affiliation: Department of Immunology and Center for Inflammation and Cancer, MD Anderson Cancer Center, Houston, Texas, USA. xyang@salud.unm.edu
authors.forename: Xuexian O
authors.initials: XO
authors.lastname: Yang
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Zhang
authors.forename: Byung-Seok
authors.initials: BS
authors.lastname: Kim
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Niu
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.forename: Romica
authors.initials: R
authors.lastname: Kerketta
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Lee
authors.forename: Seon Hee
authors.initials: SH
authors.lastname: Chang
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
authors.forename: Demin
authors.initials: D
authors.lastname: Wang
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Watowich
authors.forename: Chen
authors.identifier: 0000000200849130
authors.initials: C
authors.lastname: Dong
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D006651:Histocytochemistry; D015151:Immunoblotting; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D012313:RNA / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050791:STAT Transcription Factors / Q000276:immunology*; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D012313:RNA; D050791:STAT Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins