Control of the differentiation of regulatory T cells and TH17 cells by the DNA-binding inhibitor Id3
Copyright policy )Control of the differentiation of regulatory T cells and TH17 cells by the DNA-binding inhibitor Id3
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.
- National Institute of Health Pakistan
- Duke University United States
- National Institutes of Health United States
- University of Salford United Kingdom
- George Mason University United States
Mice, Knockout, Transcriptional Activation, Cell Differentiation, Forkhead Transcription Factors, T-Lymphocytes, Regulatory, Asthma, Mice, Inbred C57BL, Transforming Growth Factor beta1, Disease Models, Animal, Mice, Basic Helix-Loop-Helix Transcription Factors, Animals, Th17 Cells, Inhibitor of Differentiation Proteins, Promoter Regions, Genetic, Cells, Cultured, Protein Binding, Sequence Deletion
Mice, Knockout, Transcriptional Activation, Cell Differentiation, Forkhead Transcription Factors, T-Lymphocytes, Regulatory, Asthma, Mice, Inbred C57BL, Transforming Growth Factor beta1, Disease Models, Animal, Mice, Basic Helix-Loop-Helix Transcription Factors, Animals, Th17 Cells, Inhibitor of Differentiation Proteins, Promoter Regions, Genetic, Cells, Cultured, Protein Binding, Sequence Deletion
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