IgE-FcεRI protein-protein interaction as a therapeutic target against allergic asthma: An updated review

In the last decade, research has clarified the binding interactions between immunoglobulin E (IgE) and its high-affinity receptor, the FcεRI alpha chain (FcεRI). The formation of the IgE-FcεRI complex is crucial in the context of atopic allergies, linking allergen recognition to cellular activation and disease manifestation. Consequently, pharmacological strategies that disrupt these interactions are vital for managing atopic conditions. Historically, the complexity of the IgE-FcεRI binding process and challenges in producing functional recombinant derivatives has complicated data interpretation. However, advancements in structural biology, protein engineering, and immunological studies have enhanced our understanding of these protein-protein interactions (PPI), facilitating the development of more effective therapies. The introduction of anti-IgE therapies underscores the significance of the IgE-FcεRI PPI in allergic asthma. IgE, that is present locally and systemically, serves as a sensory mechanism in the adaptive immune response, particularly in mast cells (MCs) and basophils. When bound to FcεRI, IgE enables rapid memory responses to allergens, but dysregulation can lead to severe allergic asthma. Thus, the reactivity of IgE sensors can be finely modulated using various IgE-associated molecules. This review explores the mechanisms underlying IgE-dependent MC activation and its regulation by these molecules, including the latest therapeutic candidates under investigation.