Hew · Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 2015 · Observational study with spatiotemporal exposure modeling · n=256

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

Cited 145 times in the scientific literature.

Level 3 - non-randomized controlled study

Observational cohort/cross-sectional study evaluating biomarker and epigenetic outcomes across exposure windows in human subjects.

PubMed 25048800 · doi:10.1111/cea.12377 · record verified 2026-08-30

What was done

Researchers evaluated 256 children from Fresno, California, to investigate how ambient polycyclic aromatic hydrocarbon (PAH) exposure relates to immune dysfunction in atopic and non-atopic individuals. Ambient PAH concentrations were estimated using a spatial-temporal regression model over windows ranging from 24 hours to 1 year. Asthma was classified by NHLBI criteria. Regulatory T cell (Treg) function, immune cell phenotyping, protein expression (FOXP3, IL-10, IFN-γ), plasma IgE levels, and FOXP3 DNA methylation (via pyrosequencing) were measured from isolated patient samples.

What was found

Higher average PAH exposure was significantly associated with impaired Treg function and elevated methylation at the FOXP3 locus (P < 0.05, conditional on atopic status). FOXP3 hypermethylation was associated with altered FOXP3 protein expression (P < 0.001), impaired Treg function, and higher total plasma IgE levels. Increasing PAH exposure was also associated with decreased IL-10 and increased IFN-γ protein expression. The strength of these immune and epigenetic associations increased with longer exposure windows (from 24 hours up to 1 year), with similar associations detected in subjects with allergic rhinitis.

Why it matters

This study provides a plausible biological mechanism linking ambient air pollution to worsened atopic disease in children, showing that chronic PAH exposure correlates with epigenetic silencing of FOXP3 and downstream regulatory T-cell impairment.

Limits

The abstract does not report point estimates, effect sizes, or confidence intervals. Exposure was modeled from ambient spatial-temporal estimates rather than personal monitoring, which may introduce exposure misclassification. The study was conducted in a single geographic area with high pollution (Fresno, CA), and the observational design cannot confirm causality.

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