Effects Of PM2.5 On Naive T Cell Differentiation In Asthma

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness and reversible airway obstruction.Although great progress has been made in the study of the pathogenesis and treatment of asthma,the incidence and mortality of asthma are increasing in the world.The risk factors of asthma include two aspects:genetic factors(internal factors)and environmental factors(external factors).Environmental factors as an important risk factor for acute asthma and asthma attacks,including allergens,climate change and air pollution.The main cause pathogenicity of PM2.5 is due to the small particle size,large specific surface area,high activity,easy to absorb all kinds of toxic components in the air.Our preliminary study found that the concentrations of PM2.5,PM10 and other air pollutants were significantly positively correlated with the amount of respiratory diseases in children.The pathogenesis of asthma is complex,mainly divided into the following points:airway inflammation mechanism,immune and allergic airway mechanism,nerve receptor regulation mechanism,the second messenger imbalance mechanism,Thl/Th2 cell imbalance mechanism.The pathogenesis of asthma involves a variety of cells(such as eosinophils,mast cells,T lymphocytes,neutrophils and bronchial epithelial cells)and cells components,in which T cells play an important role in the regulation of immune in asthma inflammation.Most of the researches about PM2.5 in the pathogenesis of asthma focus on Thl/Th2,and less understanding of Th17/Treg.And most studies about Thl7/Treg focused on the change of single cell factor,for the research of four T cells is rare,’ and the detailed mechanism of transcriptional regulation of differentiation of T cells,especially for the key transcription regulatory factors are less studied.In this study,we first analyzed the presence of genes that were significantly associated with PM2.5 and PM10 under the action of airborne particles by the weighted gene co-expression network analysis,and then found the pathways of these genes by gene function enrichment analysis.Hypergeometric analysis finds upstream transcription factors that regulate these genes.Then,T cells were selected to verify the gene expression at the cellular level and animal level.Finally,the effect of PM2.5 on T cell differentiation in asthmatic mice was analyzed in asthmatic mice.Weighted gene co expression network analysis showed that there was significant correlation with PM2.5 and PM10 gene in the normal population,and there are pathways associated with these genes in T cells,and the key regulatory factor Stat3 was found in these genes.The results revealed that the differentiation direction of T cells to Th17 cells was significantly increased under the action of particulate pollutants.The animal experiments showed that the particulate pollutants under the action of normal lung tissues appeared serious inflammatory reaction similar to asthma;and ELISA and qPCR experiments have found that in Th17 related cytokines(IL17A and Stat3)expression was significantly up-regulated in the blood and bronchoalveolar lavage fluid.Further study in the animal model of asthma showed that under the stimulation of PM2.5,the lung tissue of asthmatic mice showed more obvious infiltration of inflammatory cells,bronchial wall thickening,pathological manifestation of mast cell hyperplasia;real-time fluorescence quantitative experiment found the expression of Tnf(Thl cytokine)was gradually increased in the three groups.Compared with the control group,the expression of Tnf was significantly different in Asthma/CMC group and Asthma/PM2.5 group,and the difference is greater in Asthma/PM2.5 group and Control group than in Asthma/CMC group and Control group.The results showed that ThO cells had a bias increase to Th17 cells under the influence of particulate contaminants in normal mice,and asthma-like inflammatory responses were observed in the lungs of mice.The experimental results show that under the influence of PM2.5 in asthma the lungs showed significant asthma inflammatory response.The effect of PM2.5 on the differentiation of T cells in asthma was analyzed by q-PCR in asthma model.The experimental results are not yet clear and require further experimental verification.This topic is of great significance for us to understand the pathogenesis of asthma and the clinical characterization of asthmatic asthma under the influence of particulate matter,so as to provide a theoretical basis and possible interventions for particles in exacerbations of asthma,has very important significance.