Activation of the aryl hydrocarbon receptor positively regulates gut migration markers on mouse B cells

Abstract

Abstract The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that links diet and environmental factors to intestinal immune function. Activation of the AhR has been shown to enhance migration to the gut by some murine CD4+ T cells with upregulated expression of CCR9. In B cells, AhR activation has been shown to suppress B cell activation and class switch recombination (CSR), but an impact on B cell migration has not been explored. Because AhR activation can enhance fecal over serum IgA levels in mice, we hypothesized that AhR activation increases B cell migration to the gut. To test this hypothesis, we examined the expression of α4β7 and CCR9 on mouse CD19+ spleen cells in vitro. Cells were activated under conditions to stimulate CSR to IgA (poly-IgD-Dextran + LPS + TGF-β), cultured with AhR ligands for 96 hours, and analyzed by flow cytometry. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (50 nM) did not change α4β7 surface expression (mean fluorescence intensity, MFI), but the MFI for CCR9 was significantly increased by 96.7% (P < 0.05) when compared to CH-223191 exposure (AhR antagonist, 100 μM). Similarly, when comparing exposure to TCDD versus CH-223191, TCDD exposure increased the percentage of α4β7+ and CCR9+ cells by 3.8% and 23.3%, respectively (P < 0.05). These results suggest that enhanced migration of B cells to the gut may be positively regulated by AhR activation. Supported by University of Northern Colorado