ADAM17-deficient mast cells exhibit decreased IgE-mediated activation due to impaired Lyn phosphorylation.

Abstract

Abstract Allergies and asthma are common ailments that are on the rise globally. Mast cells play a direct role in the signs and symptoms commonly displayed by allergic patients. The family of A Disintegrin And Metalloproteinases (ADAMs) are involved in regulating many cellular processes by cleaving surface receptors, ligands, and signaling molecules. We sought to determine the role of ADAM17 in mast cell activity. Using inhibitor-based and genetic knockout studies, loss of ADAM17 reduced mast cell degranulation. This resulted in decreased cytokine and histamine release. ADAM17MC−/− mice exhibited less severe IgE-mediated passive systemic anaphylaxis, while no difference was seen when initiated by exogenous histamine. We previously showed that ADAM17 forms a protein complex with the signaling molecule Lyn. Upon cross-linking, ADAM17−/− mast cells have reduced Lyn phosphorylation which affects downstream signaling events. ADAM17 may play a role in apical FcɛRI signaling through interactions with Lyn.