Role of the Notch ligands Jagged1 and Delta4 in Th17/Treg immune imbalance in a mouse model of chronic asthma

Asthma is associated with a T helper (Th)17/regulatory T (Treg) cells immune imbalance where the Notch signaling pathway contributes vitally. This study aimed to explore the role of Notch ligands Jagged1 and Delta4 in the Th17/Treg immune imbalance of chronic asthmatic mice.The experimental animals were randomly assigned to the Saline, ovalbumin (OVA), and OVA + γ-secretase inhibitor (GSI) groups. A mouse model of chronic asthma was induced by OVA sensitization and challenge. GSI was injected intraperitoneally before the OVA challenge in the OVA + GSI group. Lung function, lung histopathology and immunohistochemistry to assess airway inflammation, enzyme-linked immunosorbent assay to measure cytokines levels, flow cytometry to measure the proportions of Th17 (Th17%) and Treg% in CD4+T cells, quantitative real-time polymerase chain reaction and western blot to measure mRNA and protein levels of Jagged1 and Delta4 in lung tissue, and correlation analysis were performed.Lung function and histopathology and IL-4, IL-13, and IFN-γ levels in the bronchoalveolar lavage fluid (BALF) of chronic asthmatic mice showed characteristic changes of asthma. The Th17%, Th17/Treg ratio, BALF and serum IL-17 levels, and IL-17/IL-10 ratio increased significantly in the OVA group, while the Treg% and IL-10 level significantly decreased. mRNA and protein expression levels of Jagged1 and Delta4 increased significantly. GSI could reduce the Th17%, Th17/Treg ratio, IL-17, IL-17/IL-10 ratio, and Jagged1 expression in chronic asthmatic mice. The mRNA and protein levels of Jagged1 and Delta4 were positively correlated with the Th17/Treg ratio in the OVA group, while only those of Jagged1 were positively correlated with the Th17/Treg ratio in the OVA + GSI group.In chronic asthmatic mice, the Th17/Treg ratio increased, and the Notch ligands Jagged1 and Delta4 were overactive and positively regulated the Th17/Treg imbalance. GSI partially inhibited Jagged1 and relieved the Th17/Treg imbalance.