Anti-Dll4 Antibody Inhibits the Differentiation of Th17 Cells in Asthmatic Mice.

Abstract

T helper 17 (Th17) cells play an important role in allergic asthma, and the Notch ligand Delta-like ligand (Dll)4 has been reported to direct the differentiation of Th17 cells. In this study, experimental animals were divided into five groups (control group, asthma group, physiological saline group, anti-Dll4 antibody group, and immunoglobulin G group). The study aimed to explore the effect of anti-Dll4 antibody on the differentiation of Th17 cell in asthmatic mice. Dll4 protein expressions were performed by immunohistochemical imaging. The proportion of Th17 cells in mouse spleen-isolated CD4+ T cells were measured by flow cytometry. The protein expression of Th17 transcription factor retinoid-related orphan nuclear receptor (RORγt) was detected by Western blotting. Interleukin (IL)-17 levels in serum were measured by enzyme-linked immunosorbent assay (ELISA). The study found that the expression of Dll4 in lung tissue from the asthma group significantly increased compared with the anti-Dll4 antibody group. The ratio of Th17 cells in CD4+ T cells was significantly downregulated, and the protein expression of RORγt in spleen significantly reduced in the anti-Dll4 antibody group compared with the asthma group. Moreover, the IL-17 level in serum from the anti-Dll4 antibody group significantly reduced compared with the asthma group. These results suggested that anti-Dll4 antibody could inhibit the differentiation of Th17 cells in asthmatic mice.