Fine particulate air pollution epigenetically affects TET1 expression in dendritic cells and exacerbates the inflammation of Allergic Rhinitis

Abstract

Prevalence of Allergic Rhinitis(AR) is increasing year by year. It has been proved that environmental factors and epigenetic regulation are involved in the differentiation and development of immunocytes in AR. We aim to clarify whether fine particulate air pollution (for example, PM2.5) affects ten-eleven-translocation 1 (TET1) 5-mC dioxygenase enzymes in the differentiation of dentritic cells(DC) in AR. Thirty-four HDM-sensitized patients with AR and twenty healthy controls were enrolled to compare the expression of TET1 in the peripheral blood mononuclear cells(PBMCs) and DC using quantitative reverse transcription polymerase chain reaction(qRT-PCR), Western blot and flow cytometry. In vitro, monocyte-derived DCs(moDCs) exposed to PM2.5 were detected by flow cytometry to evaluate the expression costimulatory molecules. Further to co-culture DC with CD4+ T cell and evaluate the number and immunosuppressive function of activated regulatory T cell(aTreg, CD4+CD25+CD45RAlowFoxp3high) by CFSE. In vivo, BALB/c mice were OVA-sensitized and challenged with or without PM2.5 exposed. HE and PAS staining in lung tissue, cytokines in bronchoalveolar lavage fluid, serum OVA-specific IgG1 and IgE were observed. TET1 expression in lung was evaluated by qRT-PCR and flow cytometry. TET1 expression decreases in PBMC of AR patients, especially in DC. MoDCs exposed to PM2.5 highly express CD86 and downregulate the number and immunosuppressive function of aTreg, increasing Th2 polarization and decreasing TET1 expression. Exacerbating effect of PM2.5 in OVA-sensitized and challenged mice decreases the expression of TET1. Exposing to fine particulate air pollution epigenetically downregulates TET1 expression in dendritic cells and exacerbates the inflammation of Allergic Rhinitis.