Details

Autor(en) / Beteiligte

• Schones, Dustin E
• Zhao, Keji
• Liao, Wei
• Roh, Tae-Young
• Leonard, Warren J
• Cui, Yongzhi
• Oh, Jangsuk
• Cui, Kairong

Titel

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

Ist Teil von

• Nature immunology, 2008-11, Vol.9 (11), p.1288-1296

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.