Immunoglobulin E Receptor Signaling and Asthma

Elevated IgE levels and increased IgE sensitization to allergens are central features of allergic asthma. IgE binds to the high-affinity Fc epsilon receptor I (Fc epsilon RI) on mast cells, basophils, and dendritic cells and mediates the activation of these cells upon antigen-induced cross-linking of IgE-bound Fc epsilon RI. Fc epsilon RI activation proceeds through a network of signaling molecules and adaptor proteins and is negatively regulated by a number of cell surface and intracellular proteins. Therapeutic neutralization of serum IgE in moderate-to-severe allergic asthmatics reduces the frequency of asthma exacerbations through a reduction in cell surface Fc epsilon RI expression that results in decreased Fc epsilon RI activation, leading to improved asthma control. Our increasing understanding of IgE receptor signaling may lead to the development of novel therapeutics for the treatment of asthma.