Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells.

ABSTRACT: Notch and its ligands have been implicated in the regulation and differentiation of various CD4(+) T-helper cells. Regulatory T cells (T(regs)), which express the transcription factor Foxp3, suppress aberrant immune responses that are typically associated with autoimmunity or excessive inflammation. Previous studies have shown that transforming growth factor beta (TGFbeta1) induces Foxp3 expression and a regulatory phenotype in peripheral T cells. Here, we show that pharmacologic inhibition of Notch signaling using gamma-secretase inhibitor (GSI) treatment blocks (1) TGFbeta1-induced Foxp3 expression, (2) the up-regulation of Foxp3-target genes, and (3) the ability to suppress naive T-cell proliferation. In addition, the binding of Notch1, CSL, and Smad to conserved binding sites in the fo

SUBMITTER: Samon JB 

PROVIDER: S-EPMC2518888 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature