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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
FOXP3 regulates TLR10 expression in human T regulatory cells
Michael P Bell1, Phyllis A Svingen, Meher K Rahman
1Mayo Clinic, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Rochester, MN 55905, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|July 21, 2007
Summary
Human regulatory T cells express Toll-like receptor 10 (TLR10). Its expression is controlled by the transcription factor forkhead box P3 (FOXP3) and NF-AT, particularly upon T cell activation.
Area of Science:
- Immunology
- Molecular Biology
- Cellular Biology
Background:
- Toll-like receptors (TLRs) have functional relevance on human regulatory T cells (Tregs).
- The transcriptional regulation of TLRs on human Tregs remains largely uncharacterized.
- Forkhead box P3 (FOXP3) is a key transcription factor in Treg function.
Purpose of the Study:
- To investigate the hypothesis that FOXP3 regulates TLR gene expression in human Tregs.
- To elucidate the transcriptional control mechanisms of TLR10, a highly expressed TLR in human Tregs.
Main Methods:
- Quantitative PCR, Western blotting, and flow cytometry to confirm TLR10 expression in human Tregs.
- Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) to assess FOXP3 DNA binding.
- Luciferase reporter assays in Jurkat T cell lines and transfection of primary T cells to determine transcriptional regulation by FOXP3 and NF-AT.
Main Results:
- TLR10 is expressed in human Treg cells.
- FOXP3 directly binds to a cis-regulatory region near the TLR10 transcription start site.
- FOXP3 and NF-AT cooperate to transcriptionally regulate TLR10 expression, which is enhanced by TCR activation in a calcium-dependent manner.
Conclusions:
- Human Tregs express TLR10.
- FOXP3 is a key regulator of TLR10 gene transcription in human Tregs.
- Cooperative interaction between FOXP3 and NF-AT controls TLR10 expression in Tregs, influenced by T cell activation.
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