The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation

Xuexian O. Yang; Huiyuan Zhang; Byung Seok Kim; Xiaoyin Niu; Juan Peng; Yuhong Chen; Romica Kerketta; Young Hee Lee; Seon Hee Chang; David B. Corry; Demin Wang; Stephanie S. Watowich; Chen Dong

doi:10.1038/ni.2633

The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation

Xuexian O. Yang
, Huiyuan Zhang
, Byung Seok Kim
, Xiaoyin Niu
, Juan Peng
, Yuhong Chen
, Romica Kerketta
, Young Hee Lee
, Seon Hee Chang
, David B. Corry
, Demin Wang
, Stephanie S. Watowich
, Chen Dong

Immunology

Research output: Contribution to journal › Article › peer-review

120 Scopus citations

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 T_H2 and T_H9 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)
Pages (from-to)	732-740
Number of pages	9
Journal	Nature Immunology
Volume	14
Issue number	7
DOIs	https://doi.org/10.1038/ni.2633
State	Published - Jul 2013

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Flow Cytometry and Cellular Imaging Facility
Genetically Engineered Mouse Facility
Research Animal Support Facility

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10.1038/ni.2633

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@article{dae17659eac640489c00d4704bff0d6d,

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.",

author = "Yang, \{Xuexian O.\} and Huiyuan Zhang and Kim, \{Byung Seok\} and Xiaoyin Niu and Juan Peng and Yuhong Chen and Romica Kerketta and Lee, \{Young Hee\} and Chang, \{Seon Hee\} and Corry, \{David B.\} and Demin Wang and Watowich, \{Stephanie S.\} and Chen Dong",

note = "Funding Information: We thank S. Rivera and J. Parker-Thornburg of the MD Anderson Genetic Engineered Mouse Facility for help in generating gene-targeted mice; A.Y. Rudensky (Memorial Sloan-Kettering Cancer Center) for Foxp3-GFP and Foxp3-Cre mice; C.B. Wilson (University of Washington) for CD4-Cre mice; M. Kaplan (Indiana University School of Medicine) for the STAT6VT-expressing construct; and members of the Dong laboratory for help and discussion. Supported by the US National Institutes of Health (C.D., S.S.W., D.W. and D.B.C.), the Leukemia and Lymphoma Society (C.D. and D.W.), MD Anderson Cancer Center (C.D.), the Biology of Inflammation Center at Baylor College of Medicine (D.B.C.), the American Heart Association, the American Cancer Society (X.O.Y.), the Shanghai Board of Health Foundation, Shanghai Jiao Tong University (X.N.) and the Ministry of Education of China (J.P.).",

year = "2013",

month = jul,

doi = "10.1038/ni.2633",

language = "English (US)",

volume = "14",

pages = "732--740",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Research",

number = "7",

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T1 - The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation

AU - Yang, Xuexian O.

AU - Zhang, Huiyuan

AU - Kim, Byung Seok

AU - Niu, Xiaoyin

AU - Peng, Juan

AU - Chen, Yuhong

AU - Kerketta, Romica

AU - Lee, Young Hee

AU - Chang, Seon Hee

AU - Corry, David B.

AU - Wang, Demin

AU - Watowich, Stephanie S.

AU - Dong, Chen

N1 - Funding Information: We thank S. Rivera and J. Parker-Thornburg of the MD Anderson Genetic Engineered Mouse Facility for help in generating gene-targeted mice; A.Y. Rudensky (Memorial Sloan-Kettering Cancer Center) for Foxp3-GFP and Foxp3-Cre mice; C.B. Wilson (University of Washington) for CD4-Cre mice; M. Kaplan (Indiana University School of Medicine) for the STAT6VT-expressing construct; and members of the Dong laboratory for help and discussion. Supported by the US National Institutes of Health (C.D., S.S.W., D.W. and D.B.C.), the Leukemia and Lymphoma Society (C.D. and D.W.), MD Anderson Cancer Center (C.D.), the Biology of Inflammation Center at Baylor College of Medicine (D.B.C.), the American Heart Association, the American Cancer Society (X.O.Y.), the Shanghai Board of Health Foundation, Shanghai Jiao Tong University (X.N.) and the Ministry of Education of China (J.P.).

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

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DO - 10.1038/ni.2633

M3 - Article

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AN - SCOPUS:84879355943

SN - 1529-2908

VL - 14

SP - 732

EP - 740

JO - Nature Immunology

JF - Nature Immunology

IS - 7

ER -

The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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