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Previous studies have shown methylation of immune genes associate with exposure to air pollutants in pregnant women, but the cell-mediated response in the context of typical pregnancy cell alterations has not been investigated. Pregnancy causes attenuation in cell-mediated immunity with alterations in the Th1\/Th2\/Th17\/Treg environment, contributing to maternal susceptibility. We recruited women (<jats:italic>n<\/jats:italic>\u2009=\u2009186) who were 20\u00a0weeks pregnant from Fresno, CA, an area with chronically elevated AAP levels. Associations of average pollution concentration estimates for 1\u00a0week, 1\u00a0month, 3\u00a0months, and 6\u00a0months prior to blood draw were associated with Th cell subset (Th1, Th2, Th17, and Treg) percentages and methylation of CpG sites (<jats:italic>IL4<\/jats:italic>,<jats:italic>IL10, IFN\u03b3,<\/jats:italic>and<jats:italic>FoxP3<\/jats:italic>). Linear regression models were adjusted for weight, age, season, race, and asthma, using a<jats:italic>Q<\/jats:italic>value as the false-discovery-rate-adjusted<jats:italic>p<\/jats:italic>-value across all genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Short-term and mid-term AAP exposures to fine particulate matter (PM<jats:sub>2.5<\/jats:sub>), nitrogen dioxide (NO<jats:sub>2<\/jats:sub>) carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAH<jats:sub>456<\/jats:sub>) were associated with percentages of immune cells. A decrease in Th1 cell percentage was negatively associated with PM<jats:sub>2.5<\/jats:sub>(1 mo\/3 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.05), NO<jats:sub>2<\/jats:sub>(1 mo\/3 mo\/6 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.05), and PAH<jats:sub>456<\/jats:sub>(1\u00a0week\/1 mo\/3 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.05). Th2 cell percentages were negatively associated with PM<jats:sub>2.5<\/jats:sub>(1\u00a0week\/1 mo\/3 mo\/6 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.06), and NO<jats:sub>2<\/jats:sub>(1\u00a0week\/1 mo\/3 mo\/6 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.06). Th17 cell percentage was negatively associated with NO<jats:sub>2<\/jats:sub>(3 mo\/6 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.01), CO (1\u00a0week\/1 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.1), PM<jats:sub>2.5<\/jats:sub>(3 mo\/6 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.05), and PAH<jats:sub>456<\/jats:sub>(1 mo\/3 mo\/6 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.08). Methylation of the<jats:italic>IL10<\/jats:italic>gene was positively associated with CO (1\u00a0week\/1 mo\/3 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.01), NO<jats:sub>2<\/jats:sub>(1 mo\/3 mo\/6 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.08), PAH<jats:sub>456<\/jats:sub>(1\u00a0week\/1 mo\/3 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.01), and PM<jats:sub>2.5<\/jats:sub>(3 mo:<jats:italic>Q<\/jats:italic>\u2009=\u20090.06) while<jats:italic>IL4<\/jats:italic>gene methylation was positively associated with concentrations of CO (1\u00a0week\/1 mo\/3 mo\/6 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.09). Also,<jats:italic>IFN\u03b3<\/jats:italic>gene methylation was positively associated with CO (1\u00a0week\/1 mo\/3 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.05) and PAH<jats:sub>456<\/jats:sub>(1\u00a0week\/1 mo\/3 mo:<jats:italic>Q<\/jats:italic>\u2009&lt;\u20090.06).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Exposure to several AAPs was negatively associated with T-helper subsets involved in pro-inflammatory and anti-inflammatory responses during pregnancy. Methylation of<jats:italic>IL4, IL10<\/jats:italic>, and<jats:italic>IFN\u03b3 genes<\/jats:italic>with pollution exposure confirms previous research. These results offer insights into the detrimental effects of air pollution during pregnancy, the demand for more epigenetic studies, and mitigation strategies to decrease pollution exposure during pregnancy.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13148-022-01254-2","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T11:03:01Z","timestamp":1647255781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Increases in ambient air pollutants during pregnancy are linked to increases in methylation of IL4, IL10, and IFN\u03b3"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6451-0662","authenticated-orcid":false,"given":"Juan","family":"Aguilera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorui","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Balmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Lurmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Tyner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liza","family":"Lutzker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Noth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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