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

Experimental Lung Research
Zhen HeXiaoju Liu

Abstract

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 increas...Continue Reading

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