AbstractBackgroundAmbient air pollutant (AAP) exposure is associated with adverse pregnancy outcomes, such as preeclampsia, preterm labor, and low birth weight. 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 (n = 186) who were 20 weeks pregnant from Fresno, CA, an area with chronically elevated AAP levels. Associations of average pollution concentration estimates for 1 week, 1 month, 3 months, and 6 months prior to blood draw were associated with Th cell subset (Th1, Th2, Th17, and Treg) percentages and methylation of CpG sites (IL4,IL10, IFNγ,andFoxP3). Linear regression models were adjusted for weight, age, season, race, and asthma, using aQvalue as the false-discovery-rate-adjustedp-value across all genes.ResultsShort-term and mid-term AAP exposures to fine particulate matter (PM_2.5), nitrogen dioxide (NO₂) carbon monoxide (CO), and polycyclic aromatic hydrocarbons (PAH₄₅₆) were associated with percentages of immune cells. A decrease in Th1 cell percentage was negatively associated with PM_2.5(1 mo/3 mo:Q < 0.05), NO₂(1 mo/3 mo/6 mo:Q < 0.05), and PAH₄₅₆(1 week/1 mo/3 mo:Q < 0.05). Th2 cell percentages were negatively associated with PM_2.5(1 week/1 mo/3 mo/6 mo:Q < 0.06), and NO₂(1 week/1 mo/3 mo/6 mo:Q < 0.06). Th17 cell percentage was negatively associated with NO₂(3 mo/6 mo:Q < 0.01), CO (1 week/1 mo:Q < 0.1), PM_2.5(3 mo/6 mo:Q < 0.05), and PAH₄₅₆(1 mo/3 mo/6 mo:Q < 0.08). Methylation of theIL10gene was positively associated with CO (1 week/1 mo/3 mo:Q < 0.01), NO₂(1 mo/3 mo/6 mo:Q < 0.08), PAH₄₅₆(1 week/1 mo/3 mo:Q < 0.01), and PM_2.5(3 mo:Q = 0.06) whileIL4gene methylation was positively associated with concentrations of CO (1 week/1 mo/3 mo/6 mo:Q < 0.09). Also,IFNγgene methylation was positively associated with CO (1 week/1 mo/3 mo:Q < 0.05) and PAH₄₅₆(1 week/1 mo/3 mo:Q < 0.06).ConclusionExposure to several AAPs was negatively associated with T-helper subsets involved in pro-inflammatory and anti-inflammatory responses during pregnancy. Methylation ofIL4, IL10, andIFNγ geneswith 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.