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Updated: Jun 30, 2026
10:10
Development of Stem Cell-derived Antigen-specific Regulatory T Cells Against Autoimmunity
Published on: November 8, 2016
Regulatory T cells and antigen-specific tolerance
K Kretschmer1, I Apostolou, P Verginis
1Harvard Medical School, Dana-Farber Cancer Institute, Boston, Mass., USA.
Chemical Immunology and Allergy
|September 20, 2008
Summary
Foxp3-expressing regulatory T cells (Tregs) prevent autoimmune disease. Retinoic acid (RA) aids Treg conversion by counteracting costimulation
Area of Science:
- Immunology
- Molecular Biology
- Cellular Biology
Background:
- Foxp3-expressing regulatory T cells (Tregs) are crucial for preventing autoimmune diseases.
- Foxp3 transcription factor binds to numerous genes, with binding strength increasing upon stimulation.
- Treg function is linked to T-cell receptor (TCR)-dependent transcription factors.
Purpose of the Study:
- To investigate the mechanism by which retinoic acid (RA) influences Treg generation.
- To understand how RA counteracts the inhibitory effects of costimulation on extrathymic Treg conversion.
Main Methods:
- Analysis of Foxp3 binding to gene promoters.
- Investigation of gene expression changes in T-cell hybridomas after stimulation.
- Examination of the role of TCR signaling and costimulatory signals in Treg development.
- Assessment of retinoic acid's effect on AP-1 and Foxp3-NFAT transcription complexes.
Main Results:
- Foxp3 binding alone does not alter gene expression; effects become apparent after T-cell activation.
- Extrathymic Treg conversion is inhibited by costimulation, but promoted by DC-derived RA.
- RA interferes with AP-1-dependent transcription, potentially counteracting costimulation's negative impact on Treg conversion.
Conclusions:
- Retinoic acid plays a key role in promoting Treg conversion by modulating transcription factor activity.
- RA's interference with AP-1 may be the mechanism by which it overcomes costimulation-induced inhibition of Treg generation.
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