The transcription factor STAT5 is critical in dendritic cells for the development of TH 2 but not TH 1 responses

Bryan D. Bell; Masayuki Kitajima; Ryan P. Larson; Thomas A. Stoklasek; Kristen Dang; Kazuhito Sakamoto; Kay Uwe Wagner; Boris Reizis; Lothar Hennighausen; Steven F. Ziegler

doi:10.1038/ni.2541

The transcription factor STAT5 is critical in dendritic cells for the development of T_H 2 but not T_H 1 responses

Bryan D. Bell, Masayuki Kitajima, Ryan P. Larson, Thomas A. Stoklasek, Kristen Dang, Kazuhito Sakamoto, Kay Uwe Wagner, Boris Reizis, Lothar Hennighausen, Steven F. Ziegler

Eppley Institute for Cancer Research

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

162 Scopus citations

Abstract

Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T _Helper type 2 (T_H 2), but not T_H 1, allergic responses in both the skin and lungs. Loss of STAT5 in DCs led to the inability to respond to thymic stromal lymphopoietin (TSLP). STAT5 was required for TSLP-dependent DC activation, including upregulation of the expression of costimulatory molecules and chemokine production. Furthermore, T_H 2 responses in mice with DC-specific loss of STAT5 resembled those seen in mice deficient in the receptor for TSLP. Our results show that the TSLP-STAT5 axis in DCs is a critical component for the promotion of type 2 immunity at barrier surfaces.

Original language	English (US)
Pages (from-to)	364-371
Number of pages	8
Journal	Nature Immunology
Volume	14
Issue number	4
DOIs	https://doi.org/10.1038/ni.2541
State	Published - Apr 2013

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/ni.2541

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@article{e51ebe3980d14b868f2860f0464ba3f0,

title = "The transcription factor STAT5 is critical in dendritic cells for the development of TH 2 but not TH 1 responses",

abstract = "Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T Helper type 2 (TH 2), but not TH 1, allergic responses in both the skin and lungs. Loss of STAT5 in DCs led to the inability to respond to thymic stromal lymphopoietin (TSLP). STAT5 was required for TSLP-dependent DC activation, including upregulation of the expression of costimulatory molecules and chemokine production. Furthermore, TH 2 responses in mice with DC-specific loss of STAT5 resembled those seen in mice deficient in the receptor for TSLP. Our results show that the TSLP-STAT5 axis in DCs is a critical component for the promotion of type 2 immunity at barrier surfaces.",

author = "Bell, {Bryan D.} and Masayuki Kitajima and Larson, {Ryan P.} and Stoklasek, {Thomas A.} and Kristen Dang and Kazuhito Sakamoto and Wagner, {Kay Uwe} and Boris Reizis and Lothar Hennighausen and Ziegler, {Steven F.}",

note = "Funding Information: We thank I. F{\"o}rster (University of Bonn) for mice with a transgene encoding GFP in the Ccl17 locus; T. Nakayama (Chiba University) for pMX-Cre-IRES-GFP; D. Rawlings and H. Kerns (Seattle Children{\textquoteright}s Research Institute) for Btk-and Tec-deficient bone marrow; J. Hamerman and D. Campbell for discussions of the manuscript; S. Ma and W. Xu for technical support; and M. Warren and S. McCarty for administrative support. Supported by the US National Institutes of Health (R01-AI068731, R01-AR056113, R01-AR055695 and P01-HL098067 to S.F.Z., and 5T32AI007411-19 to B.D.B.).",

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T1 - The transcription factor STAT5 is critical in dendritic cells for the development of TH 2 but not TH 1 responses

AU - Bell, Bryan D.

AU - Kitajima, Masayuki

AU - Larson, Ryan P.

AU - Stoklasek, Thomas A.

AU - Dang, Kristen

AU - Sakamoto, Kazuhito

AU - Wagner, Kay Uwe

AU - Reizis, Boris

AU - Hennighausen, Lothar

AU - Ziegler, Steven F.

N1 - Funding Information: We thank I. Förster (University of Bonn) for mice with a transgene encoding GFP in the Ccl17 locus; T. Nakayama (Chiba University) for pMX-Cre-IRES-GFP; D. Rawlings and H. Kerns (Seattle Children’s Research Institute) for Btk-and Tec-deficient bone marrow; J. Hamerman and D. Campbell for discussions of the manuscript; S. Ma and W. Xu for technical support; and M. Warren and S. McCarty for administrative support. Supported by the US National Institutes of Health (R01-AI068731, R01-AR056113, R01-AR055695 and P01-HL098067 to S.F.Z., and 5T32AI007411-19 to B.D.B.).

PY - 2013/4

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N2 - Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T Helper type 2 (TH 2), but not TH 1, allergic responses in both the skin and lungs. Loss of STAT5 in DCs led to the inability to respond to thymic stromal lymphopoietin (TSLP). STAT5 was required for TSLP-dependent DC activation, including upregulation of the expression of costimulatory molecules and chemokine production. Furthermore, TH 2 responses in mice with DC-specific loss of STAT5 resembled those seen in mice deficient in the receptor for TSLP. Our results show that the TSLP-STAT5 axis in DCs is a critical component for the promotion of type 2 immunity at barrier surfaces.

AB - Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T Helper type 2 (TH 2), but not TH 1, allergic responses in both the skin and lungs. Loss of STAT5 in DCs led to the inability to respond to thymic stromal lymphopoietin (TSLP). STAT5 was required for TSLP-dependent DC activation, including upregulation of the expression of costimulatory molecules and chemokine production. Furthermore, TH 2 responses in mice with DC-specific loss of STAT5 resembled those seen in mice deficient in the receptor for TSLP. Our results show that the TSLP-STAT5 axis in DCs is a critical component for the promotion of type 2 immunity at barrier surfaces.

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The transcription factor STAT5 is critical in dendritic cells for the development of T_H 2 but not T_H 1 responses

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