Article abstract
Nature Immunology 9, 1288 - 1296 (2008)
Published online: 28 September 2008 | doi:10.1038/ni.1656
Priming for T helper type 2 differentiation by interleukin 2–mediated induction of interleukin 4 receptor 
-chain expression
Wei Liao1, Dustin E Schones1, Jangsuk Oh1, Yongzhi Cui2,3, Kairong Cui1, Tae-Young Roh1, Keji Zhao1 & Warren J Leonard1
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 
-chain (IL-4R), was essential for inducing and maintaining IL-4R expression. Although IL-4 induced IL-4R expression, T cell receptor–induced IL-4R expression was normal in Il4-/- cells but was much lower in Il2-/- cells. Notably, forced IL-4R 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.
- Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Present address: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Correspondence to: Warren J Leonard1 e-mail: wjl@helix.nih.gov
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