Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression.
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.
Liao
Wei
W
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Schones
Dustin E
DE
Oh
Jangsuk
J
Cui
Yongzhi
Y
Cui
Kairong
K
Roh
Tae-Young
TY
Zhao
Keji
K
Leonard
Warren J
WJ
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050799:STAT5 Transcription Factor / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation
D007376:Interleukin-2; D053662:Interleukin-4 Receptor alpha Subunit; D050799:STAT5 Transcription Factor