Priming for T helper type 2 differentiation by interleukin 2-mediated induction of IL-4 receptor α chain expression
| Autor: | Warren J. Leonard, Kairong Cui, Wei Liao, Dustin E. Schones, Tae-Young Roh, Keji Zhao, Yongzhi Cui, Jangsuk Oh |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Interleukin 2
Cellular differentiation Immunology Priming (immunology) Mice Transgenic Biology Article Mice Th2 Cells Downregulation and upregulation medicine STAT5 Transcription Factor Immunology and Allergy Animals Gene Interleukin 4 Regulation of gene expression Interleukin-4 Receptor alpha Subunit Cell Differentiation Molecular biology Chromatin Up-Regulation Mice Inbred C57BL Gene Expression Regulation Interleukin-2 medicine.drug |
| Zdroj: | Nature immunology |
| ISSN: | 1529-2916 1529-2908 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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