Prenatal PM2.5 exposure drives epigenetic reprogramming of fetal macrophages linked to atopic dermatitis
Abstract
Abstract Prenatal environmental exposures are increasingly recognized as contributors to atopic dermatitis (AD), yet the underlying mechanisms remain unclear. Fine particulate matter (PM 2.5 ), 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 PM 2.5 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 PM 2.5 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.
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Authors: 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, D I 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
Institutions: Ewha Womans University, Yonsei University, Ulsan College, Samsung Medical Center, University of Ulsan, Asan Medical Center, Ewha Womans University Mokdong Hospital, Freie Universität Berlin, Sungkyunkwan University, Seoul National University, Kyung Hee University, Kyungsung University, National Medical Center, Inha University, CHA University, Hallym University Sacred Heart Hospital, Inje University Sanggye Paik Hospital, CHA University Gangnam Medical Center, Kyung Hee University Dental Hospital