Dendritic cells treated with resveratrol during differentiation from monocytes gain substantial tolerogenic properties upon activation

• Published in: Immunology 2010-04, Vol.129 (4), p.525-535
• Main Authors: Švajger, Urban, Obermajer, Nataša, Jeras, Matjaž
• Format: Article
• Language: English
• Subjects: Antigens; Biomarkers - metabolism; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Proliferation - drug effects; Cells, Cultured; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Humans; immune modulation; Immune Tolerance - drug effects; Immune Tolerance - immunology; Interleukin-10 - biosynthesis; Interleukin-10 - immunology; Interleukin-12 - biosynthesis; Interleukin-12 - immunology; Lipopolysaccharides - pharmacology; Medical research; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - immunology; Monocytes - cytology; NF-kappa B - immunology; nuclear factor (NF)-кB; Original; Receptors, Cell Surface - antagonists & inhibitors; Receptors, Cell Surface - immunology; Receptors, Immunologic - antagonists & inhibitors; Receptors, Immunologic - immunology; Reference Values; regulatory T cells; Resveratrol; Stilbenes - pharmacology; T cell receptors; tolerance
• ISSN: 0019-2805; 1365-2567; 1365-2567
• DOI: 10.1111/j.1365-2567.2009.03205.x

Resveratrol is a polyphenol that acts on multiple molecular targets important for cell differentiation and activation. Dendritic cells (DCs) are a functionally diverse cell type and represent the most potent antigen-presenting cells of the immune system. In this study, we investigated resveratrol-induced effects on DCs during their differentiation and maturation. Our results show that resveratrol induces DC-associated tolerance, particularly when applied during DC differentiation. Costimulatory molecules CD40, CD80 and CD86 were down-regulated, as was the expression of major histocompatibility complex (MHC) class II molecules. Surface expression of inhibitory immunoglobulin-like transcript 3 (ILT3) and ILT4 molecules was induced, while human leucocyte antigen (HLA)-G expression was not affected. Resveratrol-treated DCs lost the ability to produce interleukin (IL)-12p70 after activation, but had an increased ability to produce IL-10. Such DCs were poor stimulators of allogeneic T cells and had lowered ability to induce CD4⁺ T-cell migration. Furthermore, treated cells were able to generate allogeneic IL-10-secreting T cells, but were not competent in inducing FoxP3 expression These tolerogenic effects are probably associated with the effect of resveratrol on multiple molecular targets through which it interferes with DC differentiation and nuclear factor (NF)-κB translocation. Our data provide new insights into the molecular and functional mechanisms of the tolerogenic effects that resveratrol exerts on DCs.