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

Journal Article (Journal Article)

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-β1 (TGF-β1)-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-β-dependent manner to control Foxp3 expression and inhibit the development of T(H)17 cells.

Full Text

Duke Authors

Cited Authors

  • Maruyama, T; Li, J; Vaque, JP; Konkel, JE; Wang, W; Zhang, B; Zhang, P; Zamarron, BF; Yu, D; Wu, Y; Zhuang, Y; Gutkind, JS; Chen, W

Published Date

  • January 2011

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 86 - 95

PubMed ID

  • 21131965

Pubmed Central ID

  • PMC3140164

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

Digital Object Identifier (DOI)

  • 10.1038/ni.1965


  • eng

Conference Location

  • United States