Vitamin C protects the spleen against PFOA-induced immunotoxicity

Perfluorooctanoic acid (PFOA) is widely used in industrial and consumer products of our daily life. It is well-documented that PFOA is closely associated with fatty liver disease. Recently, cumulating studies demonstrated the immunotoxicity of PFOA, but its harmful effect on the largest immune organ, spleen is still largely unknown. In the present study, we used PFOA-exposed mouse model together with comparative transcriptomic analysis to understand the molecular mechanisms underlying the immunotoxicity of PFOA. Furthermore, we investigated the possible use of vitamin C to reverse the PFOA-induced immunotoxicity in spleen. Our result showed that the PFOA exposure could reduce the spleen weight and plasma lymphocytes, and the splenic comparative transcriptomic analysis highlighted the alteration of cell proliferation, metabolism and immune response through the regulation of gene clusters including nicotinamide nucleotide transhydrogenases (NNT) and lymphocyte antigen 6 family member D and K (LY6D and LY6K). More importantly, the supplementation of vitamin C would relieve the PFOA-reduced spleen index and white blood cells. The bioinformatic analysis of transcriptome suggested its involvement in the spleen cell proliferation and immune response. For the first time, our study delineated the molecular mechanisms underlying the PFOA-induced immunotoxicity in the spleen. Furthermore, our results suggested that the supplementation of vitamin C had beneficial effect on the PFOA-altered spleen functions.