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

T-helper type 2 (T(H)2) cells are essential for humoral immunity and host defense. Interleukin (IL)-4 drives T(H)2 differentiation and IL-2 augments Il4 chromatin accessibility. Here we demonstrated that IL-2, by inducing STAT5 binding to the Il4ra locus, is essential for inducing and maintaining IL-4Rα expression. Although IL-4 induces IL-4Rα expression, T-cell receptor-induced IL-4Rα expression was normal in Il4(-/-) but profoundly diminished in Il2(-/-) cells. Remarkably, forced IL-4Rα expression rescued T(H)2 differentiation in Il2(-/-) cells. Moreover, genome-wide mapping by ChIP-Seq reveals broad interaction of STAT5A and STAT5B with genes associated with T(H)2 differentiation. These results reveal a previously unappreciated function for IL-2 in ‘priming’ T cells for T(H)2 differentiation and in maintaining expression of Il4ra and other genes in T(H)2-committed cells.