Aryl hydrocarbon receptor control of α4β7 and chemokine receptor 9 expression on B cells is partially determined by sex

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor that regulates immune function differentially by sex. In this study, we compared the impact of AhR activation on the expression of chemokine receptor (CCR) 9 and α4β7 integrin on male and female B cells in vitro. Splenic B cells were isolated from C57Bl/6J mice and then stimulated in culture with 300 ng/mL anti IgD-dextran, 2 ng/mL human TGF-β, and 25 μg/mL LPS. Cells were also exposed to either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, agonist, 50 nM) or CH223191 (100 μM, antagonist). After 96 hours, cells were analyzed by flow cytometry. Under antagonist conditions, the percentage of viable cells expressing CCR9 was 3.8% (male) and 5.2% (female), and α4β7 expression was 1.5% (male) and 1.6% (female) (N=6). AhR activation significantly increased (P < 0.05) the percentage of viable cells expressing either CCR9 or α4β7 by approximately 3-fold for male cells and >4-fold for female cells. Relative to males, a significant increase in the proportion of female cells expressing CCR9, but not α4β7, occurred following AhR agonism. The level of CCR9 expressed on individual cells (mean fluorescence intensity) was also significantly increased by AhR activation (approximately 50%, log scale) in both males and females, but the level of α4β7 expression was significantly increased only in female mice. These results suggest that AhR activation may enhance B cell migration into the gut preferentially in females.