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

Research output: Contribution to journalArticlepeer-review

226 Scopus citations

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.

Original languageEnglish
Pages (from-to)1288-1296
Number of pages9
JournalNature Immunology
Volume9
Issue number11
DOIs
StatePublished - 2008

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