PRIMING FOR T HELPER TYPE 2 DIFFERENTIATION BY INTERLEUKIN 2-MEDIATED INDUCTION OF INTERLEUKIN 4 RECEPTOR ALPHA-CHAIN EXPRESSION

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-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.