Prenatal PM2.5 exposure drives epigenetic reprogramming of fetal macrophages linked to atopic dermatitis.

Prenatal environmental exposures are increasingly recognized as contributors to atopic dermatitis (AD), yet the underlying mechanisms remain unclear. Fine particulate matter (PM2.5), a complex mixture of airborne pollutants, has been associated with elevated risk of allergic diseases, particularly during early development. Here we show that first-trimester PM2.5 exposure is associated with an increased risk of AD in early childhood and induces epigenetic alteration in the placenta. Integrative multi-omics analyses, including single-cell approaches, reveal hypomethylation of FCER1G in fetal macrophages, leading to its sustained overexpression. This transcriptional program persists across developmental stages and re-emerges in M2 macrophages in AD skin and peripheral blood. Functional analyses demonstrate that FCER1G-associated networks promote NADPH oxidase-mediated reactive oxygen species signaling and Th2-related inflammatory pathways. These findings suggest that prenatal PM2.5 exposure induces durable epigenetic changes in immune cells, predisposing individuals to inflammatory responses that contribute to AD pathogenesis, and highlight early-life environmental exposure as a potential target for prevention and intervention.