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Priming for Th2 differentiation requires IL-2-mediated induction of IL-4 receptor alpha chain expression


ABSTRACT: Th2 cells enable humoral immunity and host-defense to parasites. Whereas IL-4 drives Th2 differentiation and IL-2 is important later in this process by augmenting IL4 chromatin accessibility, we demonstrate that IL-2 serves an essential early role in regulating IL-4R? expression by inducing binding of Stat5a and Stat5b to the IL4ra locus, with sustained binding during Th2 differentiation. Although IL-4 induces IL-4R? expression, TCR-induced IL-4R? expression was unexpectedly normal in ILr-/- but profoundly diminished in IL2-/- T cells. Remarkably, enforced IL-4R? expression rescued Th2 differentiation in IL2-/- cells. These results reveal a novel function for IL-2, with IL-2 via Stat5 providing an early signal for IL4ra induction, thereby priming cells for Th2 differentiation and promoting/maintaining IL-4R? expression in Th2-committed cells. ChIP-seq experiments for Stat5a and Stat5b with an IgG control experiment for 8hr, 13hr and 2 rounds of Th2 differentiation. Keywords: ChIP-seq, Illumina, Th2 differentiation, Stat ChIP-seq experiments for Stat5a and Stat5b with an IgG control experiment for 8hr, 13hr and 2 rounds of Th2 differentiation. There are a total of 22 lanes of data for the three samples across the three time points.

ORGANISM(S): Mus musculus

SUBMITTER: Dustin Schones 

PROVIDER: E-GEOD-12346 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Liao Wei W   Schones Dustin E DE   Oh Jangsuk J   Cui Yongzhi Y   Cui Kairong K   Roh Tae-Young TY   Zhao Keji K   Leonard Warren J WJ  

Nature immunology 20080928 11


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(-/-)  ...[more]

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