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白细胞介素2介导白细胞介素4受体α链表达诱导促进2型辅助性T细胞分化

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

作者信息

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

机构信息

Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Nat Immunol. 2008 Nov;9(11):1288-96. doi: 10.1038/ni.1656. Epub 2008 Sep 28.

DOI:10.1038/ni.1656
PMID:18820682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2762127/
Abstract

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-4Ralpha), was essential for inducing and maintaining IL-4Ralpha expression. Although IL-4 induced IL-4Ralpha expression, T cell receptor-induced IL-4Ralpha expression was normal in Il4(-/-) cells but was much lower in Il2(-/-) cells. Notably, forced IL-4Ralpha 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.

摘要

2型辅助性T细胞（Th2）对于体液免疫和宿主防御至关重要。白细胞介素4（IL-4）驱动Th2分化，而IL-2增强Il4染色质的可及性。在此，我们证明IL-2通过诱导信号转导和转录激活因子5（STAT5）与Il4ra基因座结合，该基因座编码IL-4受体α链（IL-4Rα），对于诱导和维持IL-4Rα表达至关重要。虽然IL-4诱导IL-4Rα表达，但在Il4基因敲除（Il4-/-）细胞中，T细胞受体诱导的IL-4Rα表达正常，但在Il2基因敲除（Il2-/-）细胞中则低得多。值得注意的是，强制表达IL-4Rα可恢复Il2-/-细胞的Th2分化。此外，通过染色质免疫沉淀结合测序进行的全基因组图谱分析表明，转录因子STAT5A和STAT5B与Th2分化相关基因存在广泛相互作用。我们的结果确定了IL-2在“启动”T细胞进行Th2分化以及维持Th2定向细胞中Il4ra和其他基因表达方面以前未被认识的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/66337146c807/nihms-67297-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/7da87f62001a/nihms-67297-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/6d4a30456b0e/nihms-67297-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/9926f429aee1/nihms-67297-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/8f5b869b99b6/nihms-67297-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/66337146c807/nihms-67297-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/7da87f62001a/nihms-67297-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/6d4a30456b0e/nihms-67297-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/9926f429aee1/nihms-67297-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/8f5b869b99b6/nihms-67297-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb0/2762127/66337146c807/nihms-67297-f0008.jpg

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