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Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells.

ABSTRACT: Evidence suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased severity of atopic diseases.We hypothesized that ambient PAH exposure is linked to impairment of immunity in atopic children (defined as children with asthma and/or allergic rhinitis) from Fresno, California, an area with elevated ambient PAHs.We recruited 256 subjects from Fresno, CA. Ambient PAH concentrations (ng/m(3) ) were measured using a spatial-temporal regression model over multiple time periods. Asthma diagnosis was determined by current NHLBI criteria. Phenotyping and functional immune measurements were performed from isolated cells. For epigenetic measurements, DNA was isolated and pyrosequenced.We show that higher average PAH exposure was significantly associated with impaired Treg function and increased methylation in the forkhead box protein 3 (FOXP3) locus (P < 0.05), conditional on atopic status. These epigenetic modifications were significantly linked to differential protein expression of FOXP3 (P < 0.001). Methylation was associated with cellular functional changes, specifically Treg dysfunction, and an increase in total plasma IgE levels. Protein expression of IL-10 decreased and IFN-? increased as the extent of PAH exposure increased. The strength of the associations generally increased as the time window for average PAH exposure increased from 24 hr to 1 year, suggesting more of a chronic response. Significant associations with chronic PAH exposure and immune outcomes were also observed in subjects with allergic rhinitis.Collectively, these results demonstrate that increased ambient PAH exposure is associated with impaired systemic immunity and epigenetic modifications in a key locus involved in atopy: FOXP3, with a higher impact on atopic children. The results suggest that increased atopic clinical symptoms in children could be linked to increased PAH exposure in air pollution.

SUBMITTER: Hew KM

PROVIDER: S-EPMC4396982 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells.

Hew K M KM Walker A I AI Kohli A A Garcia M M Syed A A McDonald-Hyman C C Noth E M EM Mann J K JK Pratt B B Balmes J J Hammond S Katharine SK Eisen E A EA Nadeau K C KC

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20150101 1

<h4>Background</h4>Evidence suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased severity of atopic diseases.<h4>Objective</h4>We hypothesized that ambient PAH exposure is linked to impairment of immunity in atopic children (defined as children with asthma and/or allergic rhinitis) from Fresno, California, an area with elevated ambient PAHs.<h4>Methods</h4>We recruited 256 subjects from Fresno, CA. Ambient PAH co ...[more]

PMID: 25048800

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Project description:BackgroundEpidemiological evidence for gestational polycyclic aromatic hydrocarbon (PAH) exposure and adverse child cognitive outcomes is mixed; little is known about critical windows of exposure.ObjectiveWe investigated associations between prenatal PAH exposure and child cognition in a large, multi-site study.MethodsWe included mother-child dyads from two pooled prospective pregnancy cohorts (CANDLE and TIDES, N = 1,223) in the ECHO-PATHWAYS Consortium. Seven urinary mono-hydroxylated PAH metabolites were measured in mid-pregnancy in both cohorts as well as early and late pregnancy in TIDES. Child intelligence quotient (IQ) was assessed between ages 4-6. Associations between individual PAH metabolites and IQ were estimated with multivariable linear regression. Interaction terms were used to examine effect modification by child sex and maternal obesity. We explored associations of PAH metabolite mixtures with IQ using weighted quantile sum regression. In TIDES, we averaged PAH metabolites over three periods of pregnancy and by pregnancy period to investigate associations between PAH metabolites and IQ.ResultsIn the combined sample, PAH metabolites were not associated with IQ after full adjustment, nor did we observe associations with PAH mixtures. Tests of effect modification were null except for the association between 2-hydroxynaphthalene and IQ, which was negative in males (βmales = -0.67 [95%CI:-1.47,0.13]) and positive in females (βfemales = 0.31 [95%CI:-0.52,1.13])(pinteraction = 0.04). In analyses across pregnancy (TIDES-only), inverse associations with IQ were observed for 2-hydroxyphenanthrene averaged across pregnancy (β = -1.28 [95%CI:-2.53,-0.03]) and in early pregnancy (β = -1.14 [95%CI:-2.00,-0.28]).SignificanceIn this multi-cohort analysis, we observed limited evidence of adverse associations of early pregnancy PAHs with child IQ. Analyses in the pooled cohorts were null. However, results also indicated that utilizing more than one exposure measures across pregnancy could improve the ability to detect associations by identifying sensitive windows and improving the reliability of exposure measurement. More research with multiple timepoints of PAH assessment is warranted.

Dataset Information

Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells.

Publications

Childhood exposure to ambient polycyclic aromatic hydrocarbons is linked to epigenetic modifications and impaired systemic immunity in T cells.

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