House dust mite induced allergic airway disease is attenuated in CD11c(cre)IL-4Rα(−/l)°(x) mice

The precise mechanisms leading to development of T helper type (Th)2-driven allergic responses are unknown. We aimed to determine how IL-4 receptor alpha (IL-4Rα) signaling on CD11c(+) cells influences allergen-induced Th2 responses in mice. CD11c(cre)IL-4Rα(−/l)°(x) mice, deficient in IL-4Rα on dendritic cells and alveolar macrophages, were compared to IL-4Rα(−/l)°(x) littermate controls in models of allergic airway disease induced by OVA/alum, OVA alone or house dust mite. Cytokine responses, eosinophil and neutrophil infiltration into the lungs, airway hyperreactivity and mucus hypersecretion were evaluated after allergen challenge. In the OVA/alum model, CD11c(cre)IL-4Rα(−/lox) mice had similar airway hyperreactivity, eosinophil infiltration, Th2-type cytokine production and mucus hypersecretion to littermate controls. When alum was omitted during sensitization, CD11c(cre)IL-4Rα(−/lox) mice had similar airway hyperreactivity and mucus secretion but reduced Th2-type cytokine production and eosinophils, suggesting alum overrides the requirement for IL-4Rα signaling on CD11c(+) cells in enhancing Th2-type responses. In the house dust mite model, CD11c(cre)IL-4Rα(−/lox) mice showed similar mucus secretion, but reduced Th2 responses, eosinophils, neutrophils and airway hyperreactivity, unlike previously tested LysM(cre)IL-4Rα(−/lox) mice, which lack IL-4Rα on alveolar macrophages but not on dendritic cells. Therefore, our results indicate that IL-4Rα signaling on dendritic cells promotes allergen-induced Th2 responses and eosinophil infiltration into the lung.