Role of PD-1 signaling pathway in anti-asthmatic airway inflammation mediated by sulfatide in the asthmatic mice
Objective:To investigate the role of programmed death receptor 1(PD-1)signal pathway in anti-asthmatic airway inflammation mediated by sulfatide in a mouse model of asthma.Methods:BALB/c mice were randomly divided into the normal control group,asthma control group,asthma group with sulfatide treatment,asthma group with anti-PD-1 mAb treatment,and the asthma group with sulfa-tide plus anti-PD-1 mAb treatment(n=5).The asthmatic mice were sensitized and challenged with ovalbumin(OVA),while the rest groups were treated with the same amount of PBS.The mice in the asthma group with sulfatide treatment and the asthma group with sulfatide plus anti-PD-1 mAb treat-ment were intraperitoneally injected with sulfatide(20 μg/mouse)1 h before the first challenge,and the remaining groups were replaced with equal amounts of PBS at the corresponding time point.The asthma group with anti-PD-1 mAb treatment and the asthma group with sulfatide plus anti-PD-1 mAb treatment received intraperitoneal injections of anti-PD-1 mAb(500 μg/mouse)24 h before sulfatide treatment,and the remaining groups were replaced with equal amounts of PBS at the corresponding time point.The number of PD-1+ T cells in the lungs was detected by flow cytometry,and the air-way inflammation and the number of goblet cells in the airway were detected by HE and PAS stain-ing,respectively.The total number and different count of cells in bronchoalveolar lavage fluid(BALF)were detected by Wright-Giemsa staining,and the levels of IL-4,IL-5,IL-13,and IFN-γ in BALF and the serum OVA-specific IgE were detected by ELISA.Results:The number of goblet cells in the airway basement membrane and the total number of cells,eosinophils,and macrophages in BALF,and the levels of serum OVA-specific IgE and IL-4,IL-5,and IL-13 in BALF from the asth-ma group with anti-PD-1 mAb treatment were significantly higher than those in asthma control group(all P<0.01).The infiltration of inflammatory cells in the lung tissue of the mice treated with sulfa-tide and anti-PD-1 mAb treatment of the asthma group increased.The number of goblet cells in air-way basement membrane and the total number of cells,eosinophils and macrophages in BALF,and the levels of OVA-specific IgE in serum and IL-4,IL-5,and IL-13 in BALF from asthma group with sulfatide plus anti-PD-1 mAb treatment were significantly higher than those in sulfatide treatment of asthma group(P<0.01 or P<0.05).Additionally,the number of PD-1+T cells in the lungs from the asthma group with sulfatide treatment was significantly higher than that of the asthma control group and normal control group(all P<0.01).Conclusion:Sufatide treatment ameliorates airway in-flammation probably through activating the PD-1 signal pathway in a mouse model of asthma.
AsthmaAirway InflammationSulfatideProgrammed Death Receptor 1