Acute air pollution exposure increases TET enzymes in human PBMCs.

Abstract

Exposure to traffic-related air pollution is associated with increased morbidity and mortality. Negative health impact of diesel exhaust (DE) exposure may in part be mediated via epigenetic modulation. Ten-eleven translocation (TET) enzymes catalyze the active DNA demethylation process and play important roles in epigenetic regulation. We sought to assess the expression of TET enzymes in human PBMCs and the differentiation of immune subsets in response to acute DE exposure at a range of concentrations. Thirteen healthy participants were recruited for this randomized, double-blind, controlled human exposure study to DE. In this 4-arm crossover study, each participant was exposed for 4 hours to 3 different concentrations of DE (DE diluted to have particulate matter with a diameter of ≤2.5 micron concentration nominally set at 20, 50, and 150 μg/m³) and filtered air. Blood was collected at baseline and 4 and 24 hours after the exposure start time. The composition of PBMCs and their TET enzymes' expression were evaluated with flow cytometry. Cytokines in plasma were measured by electrochemiluminescence multiplex assays. DE exposure decreased the proportion of B cells, T_H17 cells, and activated T cells in PBMCs. TET enzymes were upregulated in PBMCs, especially in T_H1, T_H2, and T_H17 cells, at 4 hours following DE exposure. The expression of TET enzymes correlated with proinflammatory cytokine secretion in plasma. We demonstrated that acute DE exposure impacted peripheral blood leukocyte proportions and TET enzymes' expression in lymphocyte subsets at DE concentration of 50 μg/m³ and above. Our finding suggests that even a modest exposure to air pollution can impact the circulating immune cells via epigenetic modulation.