In utero exposure to per and polyfluoroalkyl substances (PFAS) associates with altered human infant T helper cell development 3101

Description Per- and polyfluoroalkyl substances (PFAS) are environmental chemical toxicants that cross the placenta during fetal development and can lead to adverse health effects in infants. There is compelling evidence of PFAS-associated immunotoxicity vis-a-vis lowered antibody responses to childhood vaccinations. However, the impact of developmental PFAS exposure on infant cellular immunity is unreported. In this study, maternal-infant dyads were enrolled in the UPSIDE-ECHO cohort during the first trimester and followed through the infant’s first year. Maternal PFAS levels were quantified in serum during the second trimester using high-performance liquid chromatography and tandem mass spectrometry. Infant lymphocyte frequencies were assessed at birth, 6 and 12 months using mass cytometry, and subpopulations were identified using a customized FlowSOM-based pipeline for high-dimensional clustering. Multivariate linear mixed-effects models were employed to assess the association between in-utero PFAS exposure and infant CD4+ T-cell subsets (n = 200). Cell-specific effects in the CD4+ T-cell compartment included lower T follicular helper cell and higher Th1, Th2, and T regulatory cell percentages with higher in-utero PFAS exposure. Importantly, effect sizes were amplified at later timepoints, indicating a persistent developmental impact. These PFAS-dependent changes in T cell subsets represent an initial step in elucidating pathways that may contribute to PFAS-related immune dysfunction. Funding Sources NIH (OD) UH3OD023349, NIH (OD) UG3OD02349, NIH (NIAID) T32AI007285, NIH (NIEHS) P30ES001247, NIH (NIEHS) R01ES036197, NIH (NICHD) R01HD083369, NIH (NCATS) University of Rochester Clinical and Translational Science Award UL1TR002001. The Wynne Center for Family Research.