Title

DIETARY AhR LIGANDS MODULATE MATURATION OF DENDRITIC CELLS

Presenter Information

Kristina Finsaas

Presentation Type

Presentation

Abstract

Via the diet, humans are exposed to a multitude of anthropogenic and natural toxicants that possess immunomodulatory properties. Dendritic cells (DCs) are critical immune cells that bridge the gap between the innate and adaptive branches of the immune system. They constitutively express the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that mediates the toxic effects of many xenobiotics. Therefore, it is important to define the impacts of dietary AhR ligands on DCs to better understand their implications on human health. We hypothesized that dietary AhR ligands, including the environmental contaminant, dioxin and the natural compounds indole-3-carbinol (I3C) and indirubin, will inhibit DC maturation. To test this hypothesis, we utilized bacterial lipopolysaccharide (LPS) to induce maturation of DC2.4 cells (a murine DC cell line) or bone marrow-derived DCs (BMDCs) and evaluated the effects of dioxin, I3C and indirubin on the expression of cell surface biomarkers including CD40, CD80 and CD86 and production of the pro-inflammatory cytokines IL-6 and TNF-?. In both DC2.4 cells and BMDCs all three AhR ligands decreased LPS-induced production of IL-6 and TNF-?. In contrast, differential effects were observed for the three dietary AhR ligands on the LPS-induced expression of cell surface molecules on both DC populations. Interestingly, following qRT-PCR analysis, upregulation of the regulatory genes IDO1, IDO2 and TGF-?3 was detected in LPS-stimulated BMDCs following exposure to dioxin, I3C and indirubin. Collectively, these results indicate that dietary exposure to these AhR ligands can inhibit DC maturation while inducing an immunoregulatory phenotype in these critical white blood cells.

Category

Life Sciences

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Apr 15th, 1:40 PM Apr 15th, 2:00 PM

DIETARY AhR LIGANDS MODULATE MATURATION OF DENDRITIC CELLS

UC 331

Via the diet, humans are exposed to a multitude of anthropogenic and natural toxicants that possess immunomodulatory properties. Dendritic cells (DCs) are critical immune cells that bridge the gap between the innate and adaptive branches of the immune system. They constitutively express the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that mediates the toxic effects of many xenobiotics. Therefore, it is important to define the impacts of dietary AhR ligands on DCs to better understand their implications on human health. We hypothesized that dietary AhR ligands, including the environmental contaminant, dioxin and the natural compounds indole-3-carbinol (I3C) and indirubin, will inhibit DC maturation. To test this hypothesis, we utilized bacterial lipopolysaccharide (LPS) to induce maturation of DC2.4 cells (a murine DC cell line) or bone marrow-derived DCs (BMDCs) and evaluated the effects of dioxin, I3C and indirubin on the expression of cell surface biomarkers including CD40, CD80 and CD86 and production of the pro-inflammatory cytokines IL-6 and TNF-?. In both DC2.4 cells and BMDCs all three AhR ligands decreased LPS-induced production of IL-6 and TNF-?. In contrast, differential effects were observed for the three dietary AhR ligands on the LPS-induced expression of cell surface molecules on both DC populations. Interestingly, following qRT-PCR analysis, upregulation of the regulatory genes IDO1, IDO2 and TGF-?3 was detected in LPS-stimulated BMDCs following exposure to dioxin, I3C and indirubin. Collectively, these results indicate that dietary exposure to these AhR ligands can inhibit DC maturation while inducing an immunoregulatory phenotype in these critical white blood cells.