Methods: BALB/c mice were challenged intranasally with Alternaria extract or PBS for 4 consecutive days following GLP-1R agonist (liraglutide) or vehicle treatment. Bronchoalveolar lavage (BAL) fluid and lungs were harvested 1 hour after the first challenge or 24 hours after the last challenge.
Results: GLP-1R agonist treatment significantly decreased IL-33 release in the BAL fluid 1 hour after the first Alternaria extract-challenge, and reduced IL-33 expression in lung epithelial cells 24 hours after the last Alternaria extract-challenge compared to vehicle treatment. Further, GLP-1R agonist treatment significantly decreased the number of IL-5 and IL-13 expressing ILC2 in the lungs challenged with Alternaria extract compared to vehicle treatment. In addition, GLP-1R agonist treatment significantly decreased IL-5, IL-13, CCL11, CCL17, CCL22 and CCL24 protein expression in the BAL fluid and lung homogenates, the number of macrophages, eosinophils and lymphocytes in the BAL fluid, perivascular eosinophil accumulation in the lung, mucus production in the bronchial epithelium, and airway responsiveness (AR) induced by Alternaria extract-challenge for 4 consecutive days.
Conclusions: These results reveal that GLP-1R signaling reduces IL-33 release, consequent ILC2 activation, and the early type-2 innate immune responses to an inhaled protease-containing aeroallergen.