Effect of Dll4-Notch signaling pathway blockade on development of Th17 cells in asthmatic mice / 中国病理生理杂志

ABSTRACT

AIM:To explore the effect of Delta-like ligand 4 (Dll4)-Notch signaling pathway blockade on the development of Thelper 17(Th17) cells in the asthmatic mice.METHODS:Male BALB/c mice were randomly divided into 5 groupscontrol group, asthma group, normal saline group, anti-Dll4 antibody group, and immunoglobulin G group.The protein expression of Dll4 was detected by immunohistochemical staining.The proportion of Th17 cells in mouse spleen isolated CD4+ T cells was measured by flow cytometry.The protein expression of Th17 transcription factor retinoid-related orphan receptor γt (RORγt) was determined by Western blot.The serum level of interleukin (IL)-17 was measured by enzyme-linked immunosorbent assay (ELISA).RESULTS:The expression of Dll4 in the lung tissues from asthma group significantly increased as compared with anti-Dll4 antibody group.The proportion of Th17 cells in CD4+ T cells was significantly down-regulated, and the protein expression of RORγt in the lung tissues was significantly reduced in anti-Dll4 antibody group compared with asthma group (P<0.05).Moreover, the serum level of IL-17 in anti-Dll4 antibody group was significantly reduced compared with asthma group (P<0.01).CONCLUSION:The blockade of Dll4-Notch signaling pathway inhibits the differentiation of Th17 cells in asthmatic mice.