Cutting edge: Smad2 and Smad4 regulate TGF-β-mediated Il9 gene expression via EZH2 displacement.

ABSTRACT: IL-9 is a proallergic cytokine produced by a newly proposed Th cell subset, Th9. Th9 cells can be generated by treatment of naive T cells with TGF-β and IL-4 in vitro. However, it is still not clear how TGF-β signaling regulates Th9 differentiation. In this study, we demonstrate that Smad2 and Smad4, two transcriptional factors activated by TGF-β signaling, are required for Th9 differentiation in vitro. Deficiency of Smad2 or Smad4 in T cells resulted in impaired IL-9 expression, which was coincident with enrichment of repressive chromatin modification histone H3 K27 trimethylation and enhanced EZH2 binding to the Il9 locus. Pharmacologic inhibition of EZH2 partially rescued IL-9 production in Smad-deficient Th9 cells. Smad proteins may displace EZH2 directly from the Il9 locus, because Sm

SUBMITTER: Wang A 

PROVIDER: S-EPMC3842015 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature