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Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells
Published on: April 16, 2012
Forkhead transcription factor FOXP3 upregulates CD25 expression through cooperation with RelA/NF-κB
Cristina Camperio1, Silvana Caristi, Giorgia Fanelli
1Department of Biology and Biotechnology Charles Darwin, University Sapienza of Rome, Rome, Italy.
Plos One
|November 13, 2012
Summary
Forkhead transcription factor FOXP3, induced by CD28 signals, cooperates with RelA to activate the CD25 gene in T cells. This interaction requires FOXP3 DNA binding and dimerization at specific promoter sites.
Area of Science:
- Immunology
- Molecular Biology
- Gene Regulation
Background:
- CD25 upregulation is characteristic of activated T cells.
- The precise regulatory mechanism of CD25 by FOXP3 remains incompletely understood.
Purpose of the Study:
- To elucidate the mechanism of CD25 gene transcriptional activation by FOXP3 in T cells.
- To investigate the synergistic role of FOXP3 and RelA in regulating CD25 expression.
Main Methods:
- Analysis of human CD4(+)CD25(-) T lymphocytes stimulated by CD28.
- Site-directed mutagenesis of the CD25 promoter regulatory region.
- Assessment of transcription factor binding and interaction using DNA-binding assays.
Main Results:
- FOXP3 and RelA synergistically activate the CD25 gene promoter.
- A regulatory region containing a κB site and two tandem FOXP3 binding sites is crucial for activation.
- Mutations in FOXP3 or κB binding sites abolish CD25 gene transactivation.
- FOXP3 dimerization and DNA binding are essential for its function as a positive activator.
Conclusions:
- FOXP3 and RelA cooperate via a specific promoter region to drive CD25 gene transcription.
- FOXP3 acts as a positive regulator of CD25, requiring both DNA binding and dimerization.
- This study reveals a novel mechanism of transcriptional regulation involving FOXP3 and RelA cooperation.
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