In vitro characterization of the role of aryl hydrocarbon receptor and bisphenol A on IL-17A regulation in mouse and human CD4+ T cells.

The objective of this investigation was to determine whether direct addition of BPA to cultured primary mouse or human naïve CD4+ T cells promotes IL-17A production and Th17 cell differentiation and to assess the role of aryl hydrocarbon receptor (AHR) in promoting IL-17A regulation. Kinetic studies showed IL-17 concentrations peaked by day 4 post-activation in the mouse and on day 6 in human CD4+ T cells under Th17 polarizing and nonpolarizing conditions. AHR activation in murine CD4+ T cells by TCDD or FICZ promoted IL-17A and IL-22 secretion compared with vehicle controls under non-Th17 polarizing conditions. In contrast, AHR antagonism by CH223191 promoted IL-17 production in human CD4+ T cells while IL-22 secretion was reduced compared with controls. AHR activation by FICZ in human CD4+ T cells decreased IL-17 while increasing IL-22 secretion. Conversely, AHR antagonism in murine CD4+ T cells suppressed IL-17A and IL-22 responses. BPA treatment of CD4+ T cells from either species did not produce a significant increase in IL-17A-positive cells or increased IL-17 secretion, whereas FICZ and CH223191 treatment induced IL-17A increases under nonpolarizing and/or polarizing conditions in CD4+ T cells from mouse and human, respectively. These studies suggest that BPA treatment of mature, naïve CD4+ T cells from either species does not induce IL-17A or IL-22 secretion, whereas AHR activation inversely regulates IL-17A responses between species. These results confirm published results showing CD4+ T cells are refractory to BPA-mediated effects on IL-17, suggesting reported BPA effects in murine CD4+ T cells may be strain-dependent.