The Role And Mechanism Of Myeloid-derived Suppressor Cells And Group 2 Innate Lymphoid Cells In Asthma

?Objective? By establishing a mouse model of asthma,we detected t Myeloidderived suppressor cell(MDSCs)and their subsets,Group 2 innate lymphoid cells(ILC2s),Th2 cells and their related cytokines in the lungs and spleen of mice to explore the effects of MDSCs,ILC2 s and Th2 on asthma mice.?Methods? Male BALB/c mice of SPF grade for 6-8 weeks were randomly divided into 3 groups(n=6-8): normal group,PBS group and asthma model group Ovalbumin(OVA)was used to establish an OVA asthma mouse model,and serum ova-specific IgE was detected by enzyme-linked immunosorbent assay(ELISA).HE staining and PAS staining were used to observe the pathological changes of lung tissues in mice.Bronchoalveolar lavage fluid(BALF)was used for cell counts and different cell counts.Flow cytometry was used to detect ILC2 s,Th1,Th2 and MDSCs levels in spleen and lung tissues.The correlation between MDSCs and ILC2 s and Th2 was analyzed.The expression of IFN-??IL-4?IL-5?IL-13?GATA3?T-bet?IL-10 and TGF-? mRNA in lung and spleen were detected by fluorescence quantitative PCR.The expression of IL-10 and TGF-? in mouse lung tissues was observed by immunohistochemistry.After MDSCs consumption by gemcitabine,flow cytometry detected the proportion and absolute value of MDSCs in the lung after MDSCs depletion,the mean fluorescence intensity of Arg1 and iNOS,and the proportion of ILC2 s,Th1 and Th2 in the lung tissues.?Results?1.Compared with the normal group and the PBS group,the asthma group had obvious airway inflammation,and HE staining of lung tissue showed obvious infiltration of inflammatory cells,thickening of the airway wall,and irregular lumen.In the PAS staining,goblet cells and mucus secretion increased significantly in the model group,serum IgE level increased,cell number in alveolar lavage fluid increased significantly,and eosinophils and neutrophils increased significantly.2.Compared with normal and PBS mice,Th1 was decreased and Th2 and ILC2 s were increased in the lung tissues of asthmatic mice.Higher expression of IL-4 and GATA3 and lower expression of IFN-? and T-bet were shown in lung and spleen cells.At the same time,the expression of IL-5 and IL-13 in the lung tissues of the asthmatic mice increased.3.The absolute amount of MDSCs in the spleen cells and lung tissues of the asthma group was significantly higher than that of the normal group and the PBS group.The expression of IL-10 in asthma mice was down-regulated in lung tissues and spleen cells,while TGF-? expression was up-regulated.4.In the lung tissue of asthmatic mice,G-MDSCs were positively correlated with ILC2.5.After MDSC depletion in gemcitabine,G-MDSCs and iNOS decreased in the drug group compared with the asthma group,but M-MDSCs did not decrease.ILC2 s and Th2 cells decreased and Th1 cells increased.?Conclusion?In the lung tissues of asthmatic mice,the proportion of ILC2 s increased,Th1/Th2 cell imbalanced,G-MDSCs were positively correlated with ILC2 s.Gemcitabine mainly deleted G-MDSCs,and the reduction of G-MDSCs reduced the inflammatory response in asthmatic mice,and reduced the proportion of ILC2 s and Th2.The highly expressed G-MDSCs,together with ILC2 s and Th2 cells,maintain and promote the inflammatory response in asthmatic mice.