Dysregulations of mucosal and systemic immune responses at adulthood after perinatal exposure to bisphenol A (BPA): possible involvement in food adverse reactions and inflammatory diseases

Oral route is the major route of exposure to the food contaminant BPA, and intestine the first organ exposed. BPA has demonstrated its ability to interfere with the gut immune system, particularly when perinatal exposure occurred. In this study, we report that adult mice perinatally exposed to a low dose of BPA [5µg/kg BW/day] showed a decrease in lysozyme activity and total IgA production in feces. These alterations were associated with a defect in dendritic cells maturation (DC) from lamina propria (LP). Frequency of these cell subsets increased in gut mucosa while it decreased in spleen, suggesting a domiciliation defect. Concomitantly, a decrease of regulatory and activated T cells in LP and mesenteric lymph node was observed. Interestingly, an alteration in the frequency of innate lymphoid cells ILC3 producing IL-22 occurred in LP associated with dysregulated IgG response against commensal bacteria in plasma. Perinatal exposure to BPA promotes inflammatory secreting profile of T cells in the spleen with an strong increase of IFN-gamma and IL-17 production. Then, BPA treatment impair intestinal immune homeostasis at adulthood, and favored inflammatory systemic immune responses. These dysregulations could participate to the increased susceptibility to food adverse reactions and to the establishment of inflammatory diseases.