Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor α-chain expression

Wei Liao; Dustin E. Schones; Jangsuk Oh; Yongzhi Cui; Kairong Cui; Tae Young Roh; Keji Zhao; Warren J. Leonard

doi:10.1038/ni.1656

Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor α-chain expression

Wei Liao, Dustin E. Schones, Jangsuk Oh, Yongzhi Cui, Kairong Cui, Tae Young Roh, Keji Zhao, Warren J. Leonard

Department of Life Science

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

230 Scopus citations

Abstract

T helper type 2 (T_H2) cells are essential for humoral immunity and host defense. Interleukin 4 (IL-4) drives T_H2 differentiation and IL-2 augments the accessibility of Il4 chromatin. Here we demonstrate that IL-2, by inducing binding of STAT5 to the Il4ra locus, which encodes IL-4 receptor α-chain (IL-4Rα), was essential for inducing and maintaining IL-4Rα expression. Although IL-4 induced IL-4Rα expression, T cell receptor-induced IL-4Rα expression was normal in Il4^-/- cells but was much lower in Il2^-/- cells. Notably, forced IL-4Rα expression restored the T_H2 differentiation of Il2^-/- cells. Moreover, genome-wide mapping by chromatin immunoprecipitation coupled with sequencing showed broad interaction of the transcription factors STAT5A and STAT5B with genes associated with T_H2 differentiation. Our results identify a previously unappreciated function for IL-2 in 'priming' T cells for T_H2 differentiation and in maintaining the expression of Il4ra and other genes in T_H2-committed cells.

Original language	English
Pages (from-to)	1288-1296
Number of pages	9
Journal	Nature Immunology
Volume	9
Issue number	11
DOIs	https://doi.org/10.1038/ni.1656
State	Published - 2008

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title = "Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor α-chain expression",

abstract = "T helper type 2 (TH2) cells are essential for humoral immunity and host defense. Interleukin 4 (IL-4) drives TH2 differentiation and IL-2 augments the accessibility of Il4 chromatin. Here we demonstrate that IL-2, by inducing binding of STAT5 to the Il4ra locus, which encodes IL-4 receptor α-chain (IL-4Rα), was essential for inducing and maintaining IL-4Rα expression. Although IL-4 induced IL-4Rα expression, T cell receptor-induced IL-4Rα expression was normal in Il4-/- cells but was much lower in Il2-/- cells. Notably, forced IL-4Rα expression restored the TH2 differentiation of Il2-/- cells. Moreover, genome-wide mapping by chromatin immunoprecipitation coupled with sequencing showed broad interaction of the transcription factors STAT5A and STAT5B with genes associated with TH2 differentiation. Our results identify a previously unappreciated function for IL-2 in 'priming' T cells for TH2 differentiation and in maintaining the expression of Il4ra and other genes in TH2-committed cells.",

author = "Wei Liao and Schones, {Dustin E.} and Jangsuk Oh and Yongzhi Cui and Kairong Cui and Roh, {Tae Young} and Keji Zhao and Leonard, {Warren J.}",

year = "2008",

doi = "10.1038/ni.1656",

language = "English",

volume = "9",

pages = "1288--1296",

journal = "Nature Immunology",

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T1 - Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor α-chain expression

AU - Liao, Wei

AU - Schones, Dustin E.

AU - Oh, Jangsuk

AU - Cui, Yongzhi

AU - Cui, Kairong

AU - Roh, Tae Young

AU - Zhao, Keji

AU - Leonard, Warren J.

PY - 2008

Y1 - 2008

N2 - T helper type 2 (TH2) cells are essential for humoral immunity and host defense. Interleukin 4 (IL-4) drives TH2 differentiation and IL-2 augments the accessibility of Il4 chromatin. Here we demonstrate that IL-2, by inducing binding of STAT5 to the Il4ra locus, which encodes IL-4 receptor α-chain (IL-4Rα), was essential for inducing and maintaining IL-4Rα expression. Although IL-4 induced IL-4Rα expression, T cell receptor-induced IL-4Rα expression was normal in Il4-/- cells but was much lower in Il2-/- cells. Notably, forced IL-4Rα expression restored the TH2 differentiation of Il2-/- cells. Moreover, genome-wide mapping by chromatin immunoprecipitation coupled with sequencing showed broad interaction of the transcription factors STAT5A and STAT5B with genes associated with TH2 differentiation. Our results identify a previously unappreciated function for IL-2 in 'priming' T cells for TH2 differentiation and in maintaining the expression of Il4ra and other genes in TH2-committed cells.

AB - T helper type 2 (TH2) cells are essential for humoral immunity and host defense. Interleukin 4 (IL-4) drives TH2 differentiation and IL-2 augments the accessibility of Il4 chromatin. Here we demonstrate that IL-2, by inducing binding of STAT5 to the Il4ra locus, which encodes IL-4 receptor α-chain (IL-4Rα), was essential for inducing and maintaining IL-4Rα expression. Although IL-4 induced IL-4Rα expression, T cell receptor-induced IL-4Rα expression was normal in Il4-/- cells but was much lower in Il2-/- cells. Notably, forced IL-4Rα expression restored the TH2 differentiation of Il2-/- cells. Moreover, genome-wide mapping by chromatin immunoprecipitation coupled with sequencing showed broad interaction of the transcription factors STAT5A and STAT5B with genes associated with TH2 differentiation. Our results identify a previously unappreciated function for IL-2 in 'priming' T cells for TH2 differentiation and in maintaining the expression of Il4ra and other genes in TH2-committed cells.

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DO - 10.1038/ni.1656

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SN - 1529-2908

VL - 9

SP - 1288

EP - 1296

JO - Nature Immunology

JF - Nature Immunology

IS - 11

ER -

Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor α-chain expression

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