Dae Yeol Yang, Song-I Yang, Yong Joo Park, Seung-Hwa Lee, Hwan-Cheol Kim, Somi Lim, Maike Herkenrath, Ah-Yoon Song, Jeong-Hyun Kim, Hyo-Bin Kim, Eom Ji Choi, Youn Ho Shin, Kyung Won Kim, Ji Soo Park, Dong In Suh, Jihyun Kim, Kangmo Ahn, Suk-Joo Choi, Soo-Young Oh, Ja-Young Kwon, Soo Hyun Kim, Jong Kwan Jun, Mi-Young Lee, Hye-Sung Won, Kwoneel Kim, Soo-Jong Hong
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.