Myeloid cell-specific IL4Rα deletion protects against mixed allergen-induced lung injury in mice

Abstract

Abstract Introduction IL-4 and IL-13 play an essential role in the pathogenicity of allergic asthma via the common receptor, i.e., IL4Rα. However, the myeloid cell-specific role of IL4Rα-mediated signaling in allergic asthma has remained unclear. We hypothesized that myeloid cell-specific IL4Rα signaling is essential for granulocytic inflammation and associated pathological outcomes. Methods Myeloid cell-specific IL4Rα-deficient (LysMCRE/CRE/IL4RαFl/Fl) and control (LysMCRE/CRE/IL4RαWT/WT) mice were exposed to mixed allergens, and total and differential cell counts were performed on bronchoalveolar lavage fluid. Unlavaged left lung lobe was fixed in 10% formalin and used for lung pathology assessment. Results In contrast to mixed allergen-exposed control mice that had exaggerated immune cell recruitment, myeloid cell-specific IL4Rα-deficient mice had significantly reduced immune cell infiltration into the lung airspaces. The reduction in immune cell infiltration in myeloid cell-specific IL4Rα-deficient mice was attributable to a significant decrease in eosinophils and lymphocytes. Additionally, while mixed allergen-exposed control mice exhibited pronounced lung inflammation and consolidation, myeloid cell-specific IL4Rα deletion significantly ameliorates lung pathology. Mucous cell metaplasia (MCM), another key feature of allergic asthma, was unaltered in myeloid cell-specific IL4Rα-deficient mice suggesting its dispensable role in mixed allergen-induced MCM. Conclusion Collectively, our data show that myeloid cell-specific IL4Rα signaling plays an indispensable role in immune cell recruitment specifically eosinophils, and its deletion protects against mixed allergen-induced lung injury. Supported by grants from NIEHS (R01 ES030125) and NIGMS (P20 GM130555-6611)