Elevated ozone activates maternal immunity to drive offspring IgG-mediated anaphylaxis through IgG glycosylation alterations.

Global allergic disease burden is rising, driven by environmental factors like ozone (O3)-induced oxidative stress. Epidemiological studies have linked prenatal oxidative stress to offspring allergy susceptibility, but causality remains unproven. Here, our retrospective analysis including 5,299 pregnancies postulates that mid-to-late gestational O3 exposure triggers maternal immune activation (MIA), increasing neutrophil/monocyte abnormality risks. Using an animal model of prenatal O3 exposure-induced MIA, we demonstrate that offspring of MIA dams-especially males-exhibit heightened allergy susceptibility. Mechanistically, MIA disrupts maternal-fetal IgG transfer and neonatal glycosylation, particularly Mgat3-mediated N-acetylglucosamine (GlcNAc) modifications. This perturbation preferentially activates juvenile male IL-17/TNF signaling. In adulthood, downstream transcription factors c-Jun/c-Fos activate Mgat4a to sustain GlcNAc glycosylation. This glycosylation of IgG is associated with enhanced IgG-FcγRIII affinity and more severe inflammatory responses during anaphylaxis. Our study bridges environmental epidemiology, immunology, and glycobiology to suggest how prenatal oxidative stress reprograms offspring immunity, offering insights into developmental origins of allergic diseases.