Control of the differentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor Id3.

ABSTRACT: The molecular mechanisms that direct transcription of the gene encoding the transcription factor Foxp3 in CD4(+) T cells remain ill-defined. We show here that deletion of the DNA-binding inhibitor Id3 resulted in the defective generation of Foxp3(+) regulatory T cells (T(reg) cells). We identify two transforming growth factor-?1 (TGF-?1)-dependent mechanisms that were vital for activation of Foxp3 transcription and were defective in Id3(-/-) CD4(+) T cells. Enhanced binding of the transcription factor E2A to the Foxp3 promoter promoted Foxp3 transcription. Id3 was required for relief of inhibition by the transcription factor GATA-3 at the Foxp3 promoter. Furthermore, Id3(-/-) T cells showed greater differentiation into the T(H)17 subset of helper T cells in vitro and in a mouse asthma model. Therefore, a network of factors acts in a TGF-?-dependent manner to control Foxp3 expression and inhibit the development of T(H)17 cells.

SUBMITTER: Maruyama T 

PROVIDER: S-EPMC3140164 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature