Integrative omics analyses uncover the mechanism underlying the immunotoxicity of perfluorooctanesulfonate in human lymphocytes

Perfluorooctanesulfonate (PFOS) is a man-made chemical widely used in industrial products. Due to its high persistence, PFOS has been detected in most animal species including the human population, wild animals, and aquatic organisms. Both cross-sectional studies and laboratory animal studies have shown hepatotoxicity, renal toxicity, and reproductive toxicity caused by PFOS exposure. Recently, a limited number of PFOS studies have raised concerns about its potential immune system effects. However, the molecular mechanism underlying the immunotoxicity of PFOS remains unknown. In this study, we used primary human lymphocytes as a model, together with integrative omics analyses, including the transcriptome and lipidome, and bioinformatics analysis, to resolve the immune toxicity effects of PFOS. Our results demonstrated that PFOS could alter the production of interleukins in human lymphocytes. Additionally, PFOS exposure could dysregulate clusters of genes and lipids that play important roles in immune functions, such as lymphocyte differentiation, inflammatory response, and immune response. The findings of this study offer novel insight into the molecular mechanisms underlying the immunotoxicity of PFOS, and open the potential of using the identified PFOS-responsive genes and lipids as biomarkers for risk assessment.