Priming for Th2 differentiation requires IL-2-mediated induction of IL-4 receptor alpha chain expression
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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-4Rα expression by inducing binding of Stat5a and Stat5b to the IL4ra locus, with sustained binding during Th2 differentiation. Although IL-4 induces IL-4Rα expression, TCR-induced IL-4Rα expression was unexpectedly normal in ILr-/- but profoundly diminished in IL2-/- T cells. Remarkably, enforced IL-4Rα 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-4Rα 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
ORGANISM(S): Mus musculus
PROVIDER: GSE12346 | GEO | 2008/12/11
SECONDARY ACCESSION(S): PRJNA113171
REPOSITORIES: GEO
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