PFOS+PFOA exposure alters Th1/Th17/Th22 and Th2 responses in Poly(I:C)-induced murine lung inflammation

Pulmonary inflammation, often triggered by environmental factors, involves complex immune responses, particularly those mediated by T helper (Th) cell subsets. Interleukin-17 (IL-17) signaling is a key pathway in chronic allergic pulmonary inflammation, influencing oxidative stress and airway remodeling. Per- and polyfluoroalkyl substances (PFAS) like PFOS and PFOA are widespread environmental contaminants, but their specific impact on IL-17-related immune regulation in the lung, especially under inflammatory challenge, remains underexplored. Understanding this interaction is crucial for assessing PFAS immunotoxicity.

Researchers investigated the effects of PFOS+PFOA co-exposure on IL-17-related immune responses and Poly(I:C)-induced lung inflammation. 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, focusing on T helper cell percentages and gene expression related to the IL-17 pathway.

Poly(I:C) stimulation significantly increased Th1, Th17, and Th22 cell percentages, consistent with robust immune activation.

PFOS+PFOA exposure dose-dependently attenuated these Th1, Th17, and Th22 responses under Poly(I:C) (+) conditions, indicating an immunosuppressive effect on these pro-inflammatory subsets. Conversely, increased Th2 cell percentages were observed in the PFOS+PFOA exposure groups, suggesting a shift towards a Th2-dominant immune profile. Gene expression analyses of Stat3, Il17ra, and Ror-γt further supported tissue-level modulation of IL-17-related signaling pathways. These findings collectively demonstrate that PFOS+PFOA exposure can significantly alter the pulmonary immune microenvironment and modify Th1/Th17/Th22-associated responses to inflammatory stimuli.