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

First Author  Maruyama T Year  2011
Journal  Nat Immunol Volume  12
Issue  1 Pages  86-95
PubMed ID  21131965 Mgi Jnum  J:167447
Mgi Id  MGI:4868301 Doi  10.1038/ni.1965
Citation  Maruyama T, et al. (2011) Control of the differentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor Id3. Nat Immunol 12(1):86-95
abstractText  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-beta1 (TGF-beta1)-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-beta-dependent manner to control Foxp3 expression and inhibit the development of T(H)17 cells.
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