Traffic-related PM2.5 and Diverse Constituents Disturb the Balance of Th17/Treg Cells by STAT3/RORγt-STAT5/Foxp3 Signaling Pathway in a Rat Model of Asthma.

Water-soluble ions (WSI) and organic extract (OE) in traffic-related particulate matter with aerodynamic diameters <= 2.5 mu m (TRPM2.5) are potential risk factors for asthma exacerbation. Although CD4(+) T lymphocytes mediated immune response is involved in the pathogenesis of asthma, the effect of WSI-TRPM2.5 and OE-TRPM2.5 on the balance of Th17/Treg cells in asthma remains poorly understood. In this study, the ovalbumin (OVA)sensitized rats were repeatedly exposure to TRPM2.5 (3 mg/kg.bw), WSI-TRPM2.5 (1.8 mg/kg.bw, 7.2 mg/kg.bw) and OE-TRPM2.5 (0.6 mg/kg.bw, 2.4 mg/kg.bw) every three days for five times. The inflammation response and hyperemia edema were observed in the lung and trachea tissues. DNA methylation levels of STAT3 and ROR gamma t genes in rats with WSI-TRPM2.5 and OE-TRPM2.5 treatment were decreased. DNA methylation level in STAT5 gene tended to decrease, with no change observed on Foxp3 expression. WSI-TRPM2.5 and OE-TRPM2.5 enhanced the mRNA and protein expression of STAT3 and ROR gamma t while inhibited the expression of STAT5 and Foxp3, which may contribute to the imbalance of Th17/Treg cells (P < 0.05). More importantly, recovered balance of Th17/Treg cell subsets, upregulated p-STAT5 and Foxp3 expression and reduced p-STAT3 and ROR gamma t levels were observed after 5-Aza treatment. Our results demonstrate that the STAT3/ROR gamma t-STAT5/Foxp3 signaling pathway is involved in asthma exacerbation induced by WSI-TRPM2.5 and OE-TRPM2.5 through disrupting the balance of Th17/Treg cells. The alteration of DNA methylation of STAT3, STAT5, and ROR gamma t genes may be involved in asthma exacerbation as well.