Opposing Roles for Lyn and Fyn Kinases in Mast Cell IgG Receptor Signaling (139.4)

Abstract

Abstract Mast cells are key players of the innate immune system. In addition to their role in atopic disease, mast cell involvement is strongly suspected in inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, and atherosclerosis. Once activated, they degranulate and produce cytokines, resulting in the recruitment of other immune cells. It is well-appreciated that mast cells are activated via the high-affinity immunoglobulin E (IgE) receptor FceRI. In this study we focus on mast cell activation via the immunoglobulin G (IgG) receptor FcγRII/RIII and downstream signaling by Fyn and Lyn kinases. Lyn-deficient mast cells displayed increased histamine and leukotriene C4 secretion, but no change in cytokine production, suggesting a restricted and negative regulatory role for Lyn kinase in mast cell IgG signaling. In contrast, we show that Fyn kinase is required for IgG-mediated histamine, LTC4, and cytokine production in mast cells, and has a similar role in basophils and macrophages. These data illustrate the importance of Src family kinases in IgG signaling, a means by which mast cells may be activated in chronic inflammatory diseases. Supported by NIH grants 1R01 AI59638 and U19A1077435.