Investigation of the Effects of Perfluorooctane Sulfonic Acid (PFOS) and Perfluorooctanoic Acid (PFOA) Exposure on Interleukin‐17 Signalling and Poly(I:C)‐Induced Lung Inflammation in BALB/c Mice

The aim of this study was to investigate the effects of co-exposure to perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) on the IL-17-related immune responses and the Poly(I:C)-induced lung inflammation. A total of 66 adult male BALB/c mice were divided into 11 groups, including controls, dose groups receiving PFOS+PFOA (1, 3, 9 mg/kg/day), and combination groups challenged with intratracheal Poly(I:C). Immunological responses were evaluated using flow cytometry, RT-qPCR and ELISA assays. Poly(I:C) stimulation increased Th1, Th17 and Th22 cell percentages, consistent with immune activation. PFOS+PFOA exposure attenuated these responses in a dose-dependent manner under Poly(I:C) (+) conditions. Conversely, increased Th2 cell percentages were observed in PFOS+PFOA exposure groups. Gene expression analyses of Stat3, Il17ra and Ror-γt further suggested tissue-level modulation of IL-17-related signalling pathways. Overall, PFOS+PFOA exposure may modulate the pulmonary immune microenvironment and alter Th1/Th17/Th22-associated responses to Poly(I:C)-induced inflammatory stimulation. These findings suggest that PFAS mixtures may influence pulmonary immune regulation under inflammatory conditions and support the inclusion of immune endpoints in PFAS toxicological evaluation.