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In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
Published on: December 30, 2016
Molecular mechanisms underlying FOXP3 induction in human T cells
Pierre-Yves Mantel1, Nadia Ouaked, Beate Rückert
1Swiss Institute of Allergy and Asthma Research, Obere Str. 22, CH-7270 Davos, Switzerland.
Journal of Immunology (Baltimore, Md. : 1950)
|March 7, 2006
Summary
This study reveals the human FOXP3 promoter structure and identifies key regulators for T regulatory cell induction, crucial for immune tolerance. Cyclosporin A inhibits FOXP3 expression, unlike other immunosuppressants.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- FOXP3 is essential for T regulatory cells and immune tolerance.
- Pathways regulating FOXP3 induction remain unclear.
Purpose of the Study:
- To elucidate the structure and function of the human FOXP3 promoter.
- To identify molecular mechanisms controlling FOXP3 induction.
Main Methods:
- Rapid Amplification of cDNA Ends (RACE) to define the promoter.
- Reporter-gene constructs in primary human T cells.
- Analysis of FOXP3 expression, mRNA, and protein levels.
Main Results:
- Identified a T cell-specific basal promoter with TATA and CAAT boxes.
- Discovered six NF-AT and AP-1 binding sites regulating FOXP3 transactivation.
- Observed FOXP3 induction upon TCR engagement, suppressed by cyclosporin A.
Conclusions:
- The study reveals the human FOXP3 promoter structure and induction mechanisms.
- Identified positive regulators of FOXP3 and highlighted cyclosporin A as an inhibitor.
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