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 (Treg cells). We identify two transforming growth factor-β 21 (TGF-β 21)-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 TH 17 subset of helper T cells in vitro and in a mouse asthma model. Therefore, a network of factors acts in a TGF-β 2-dependent manner to control Foxp3 expression and inhibit the development of TH 17 cells.
|Number of pages||10|
|Publication status||Published - 2011 Jan|
ASJC Scopus subject areas
- Immunology and Allergy