FcεRI: A Master Regulator of Mast Cell Functions

Mast cells (MCs) perform multiple functions thought to underlie different manifestations of allergies. Various aspects of antigens (Ags) and their interactions with immunoglobulin E (IgE) cause diverse responses in MCs. Fc epsilon RI, a high-affinity IgE receptor, deciphers the Ag-IgE interaction and drives allergic responses. Fc epsilon RI clustering is essential for signal transduction and, therefore, determines the quality of MC responses. Ag properties precisely regulate Fc epsilon RI dynamics, which consequently initiates differential outcomes by switching the intracellular-signaling pathway, suggesting that Ag properties can control MC responses, both qualitatively and quantitatively. Thus, the therapeutic benefits of Fc epsilon RI-targeting strategies have long been examined. Disrupting IgE-Fc epsilon RI interactions is a potential therapeutic strategy because the binding affinity between IgE and Fc epsilon RI is extremely high. Specifically, Fc epsilon RI desensitization, due to internalization, is also a potential therapeutic target that is involved in the mechanisms of allergen-specific immunotherapy. Several recent findings have suggested that silent internalization is strongly associated with Fc epsilon RI dynamics. A comprehensive understanding of the role of Fc epsilon RI may lead to the development of novel therapies for allergies. Here, we review the qualitatively diverse responses of MCs that impact the attenuation/development of allergies with a focus on the role of Fc epsilon RI toward Ag exposure.