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Generation of Immature, Mature and Tolerogenic Dendritic Cells with Differing Metabolic Phenotypes
Published on: June 22, 2016
TGFbeta-dependent gene expression profile during maturation of dendritic cells
O Fainaru1, T Shay, S Hantisteanu
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Genes and Immunity
|March 3, 2007
Summary
Transforming growth factor beta (TGFbeta) modulates dendritic cell (DC) maturation by altering specific gene expression. TGFbeta downregulates interleukin-12 while upregulating interleukin-18 and peroxisome proliferator-activated receptor gamma (PPARgamma).
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Dendritic cells (DCs) are crucial for initiating immune responses through maturation.
- Bacterial lipopolysaccharide (LPS) strongly induces DC maturation.
- Transforming growth factor beta (TGFbeta) can inhibit DC maturation.
Purpose of the Study:
- To investigate global gene expression patterns in DCs treated with LPS and TGFbeta.
- To identify genes modulated by TGFbeta during LPS-induced DC maturation.
- To elucidate the role of TGFbeta in regulating key inflammatory mediators and receptors.
Main Methods:
- Global gene expression profiling of bone marrow-derived DCs.
- Treatment of DCs with LPS and TGFbeta.
- Quantitative analysis of specific cytokine and receptor gene expression.
Main Results:
- LPS induced significant changes in DC gene expression.
- TGFbeta selectively modulated a subset of LPS-responsive genes.
- TGFbeta downregulated interleukin-12 (IL-12) and upregulated interleukin-18 (IL-18) expression.
- TGFbeta increased peroxisome proliferator-activated receptor gamma (PPARgamma) expression, correlating with decreased chemokine receptor 7 (CCR7) expression.
Conclusions:
- TGFbeta significantly influences DC maturation by altering specific inflammatory gene expression.
- TGFbeta's inhibitory effect on DC maturation involves differential regulation of IL-12 and IL-18.
- PPARgamma may mediate TGFbeta-induced suppression of CCR7 expression in DCs.
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