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

被引：231

作者：

Liao, Wei ^{[1
]}

Schones, Dustin E. ^{[1
]}

Oh, Jangsuk ^{[1
]}

Cui, Yongzhi ^{[2
]}

Cui, Kairong ^{[1
]}

Roh, Tae-Young ^{[1
]}

Zhao, Keji ^{[1
]}

Leonard, Warren J. ^{[1
]}

机构：

[1] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA

[2] NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 11期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/ni.1656

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

T helper type 2 (T(H)2) cells are essential for humoral immunity and host defense. Interleukin 4 (IL-4) drives T(H)2 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 alpha-chain (IL-4R alpha), was essential for inducing and maintaining IL-4R alpha expression. Although IL-4 induced IL-4R alpha expression, T cell receptor-induced IL-4R alpha expression was normal in Il4(-/-) cells but was much lower in Il2(-/-) cells. Notably, forced IL-4R alpha expression restored the T(H)2 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(H)2 differentiation. Our results identify a previously unappreciated function for IL-2 in 'priming' T cells for T(H)2 differentiation and in maintaining the expression of Il4ra and other genes in T(H)2-committed cells.

引用

页码：1288 / 1296

页数：9

共 41 条

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