Cutting edge: TGF-beta inhibits Th type 2 development through inhibition of GATA-3 expression.

TGF-beta is an important immunomodulatory cytokine that can inhibit differentiation of effector T cells. In this report, we address the molecular mechanisms through which TGF-beta inhibits differentiation of CD4(+) cells into Th type 2 cells. We demonstrate that TGF-beta inhibits GATA-3 expression in developing Th cells. We also show that inhibition of GATA-3 expression by TGF-beta is a major mechanism of inhibition of Th2 differentiation by TGF-beta as ectopic expression of GATA-3 in developing T cells overcomes the ability of TGF-beta to inhibit Th2 differentiation. TGF-beta likely inhibits GATA-3 expression at the transcriptional level and does so without interfering with IL-4 signaling.