IgE receptor signaling in food allergy pathogenesis (1)
Food allergy is an immunological disorder characterized by dysregulated responses and the development of immediate hypersensitivity reactions to ingested foods.
IgE binds to two main receptors, the high affinity FcεRI and the low affinity FcεRII. These receptors have set expression patterns, with FcεRI primarily on mast cells, basophils and dendritic cells. Crosslinking of FcεRI by IgE and allergen results in initiation of signaling via the immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic tail of the receptor, leading to both degranulation and cytokine gene transcription.
Studies in murine models have established obligate roles for IgE, FcεRI, Syk, and mast cells in the onset of immediate hypersensitivity reactions and anaphylaxis following acute food allergen challenge in sensitized animals.
While mast cell activation may directly promote Th2 induction, B cell switching to IgE and other aspects of the allergic response, the ability to disrupt Treg induction and function may be the most critical mast cell effect.
Neutralization of IgE or inhibition of mast cells might have the added, unanticipated benefit of favoring the restoration of tolerance and Treg-dominated immune responses. Mice treated with anti-IgE during desensitization therapy regained Treg-dominated responses to allergen and showed reductions in Th2 cells.