The role of particulate matters on methylation of IFN-γ and IL-4 promoter genes in pediatric allergic rhinitis

Abstract

Allergic rhinitis (AR) is a chronic inflammatory disorder driven by T cell activation. How particulate matter contributes to epigenetic changes that in turn influence cytokine gene expression in CD4⁺T cells remains unclear. In this study, 105 children diagnosed with AR and 90 healthy controls were recruited to explore the possible mechanism of particulate matter (PM) on the epigenetic regulation of CD4⁺T IFN-γ and IL-4 promoter genes. Daily average PM₁₀ and PM_2.5 were obtained from five state-controlled monitoring stations, and activity-based dynamic exposure and personal exposure data were collected. DNA methylation patterns of IFN-γ and IL-4 promoter regions were analyzed using bisulfite sequencing. mRNA levels were detected by real-time quantitative reverse transcription polymerase chain reaction. We found that the methylation rate in IFN-γ was higher in AR CD4⁺T cells than in the controls. IFN-γ mRNA expression was significantly decreased in CD4⁺T cells, and negatively correlated with the mean methylation level of IFN-γ. However, no correlation between IL-4 methylation and IL-4 mRNA expression was found. After adjusting for age, gender, exclusive breastfeeding within 4 months after birth and parental history of allergic disease, out data showed that PM_2.5 exposure level was positively correlated with methylation level in IFN-γ promoter region and decreased cytokine expression. We conclude that the effect of PM_2.5 on pediatric AR may be mediated through epigenetic modification of IFN-γ promoter region.