iNOS/Arg-1 balance and sIgA levels are associated with intestinal mucosal immune defense in children chronically exposed to air pollutants and lead.

BACKGROUND: Air pollutants and lead (Pb) are widespread environmental risk factors that may disrupt children's intestinal immune homeostasis. However, the immunoregulatory responses of intestinal mucosal immunity to chronic co-exposure remain poorly understood. METHODS: We conducted a cross-sectional study of 238 children aged 3-6 years from an e-waste recycling area (Guiyu) and a reference area (Haojiang). Estimated average daily doses (ADDs) of air pollutants and blood Pb levels were assessed. Peripheral blood cells, serum cytokines, macrophage polarization markers, including inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1), and serum secretory immunoglobulin A (sIgA) were measured. Single-pollutant regression, Bayesian kernel machine regression, and restricted cubic spline analyses were performed. Network toxicology was used to explore potential molecular targets and immune-related pathways. RESULTS: Children from Guiyu had higher blood Pb levels and higher ADDs of PM2.5, PM10, NO2, SO2, and CO. They also showed increased lymphocyte and monocyte counts, decreased iNOS, increased Arg-1 and IL-4, and a lower iNOS/Arg-1 ratio. Mixed exposure was inversely associated with iNOS/Arg-1 ratio. Serum sIgA levels did not differ significantly between areas, and mixed exposure was not directly associated with serum sIgA; however, a nonlinear association was observed between the iNOS/Arg-1 ratio and serum sIgA. Network toxicology implicated inflammatory signaling, oxidative stress, nitric oxide biosynthesis, arginine metabolism, and IgA-related intestinal immune pathways. CONCLUSIONS: Long-term co-exposure to air pollutants and Pb was associated with a lower iNOS/Arg-1 ratio and an M2-like macrophage polarization-related marker profile in children. The observed nonlinear association between the iNOS/Arg-1 ratio and sIgA may reflect a potential relationship between macrophage polarization-related immune responses and sIgA-associated mucosal immunity. These findings highlight pollutant-associated immune alterations related to intestinal mucosal defense.