The Role of the High-Affinity IgE Receptor, FcεRI, in Eosinophilic Gastrointestinal Diseases

Primary eosinophilic gastrointestinal diseases (EGIDs) are a heterogeneous group of diseases including eosinophilic esophagitis, eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilic enteritis, and eosinophilic colitis. The unifying hallmark and diagnostic marker of EGIDs is an eosinophil-rich inflammatory infiltrate of the GI mucosa, in the absence of known causes for eosinophilia. The etiology of EGIDs is not yet fully understood. The pathogenesis however seems to involve a complex interplay of genetic predisposition, exposure to food- and environmental allergens and IgE-mediated activation of the immune system. Accumulating evidence relates EGIDs to the group of T-helper (Th) 2 mediated immune disorders, like IgE-mediated allergy. In this article we discuss a possible role of IgE-mediated immune-activation via the high affinity receptor for IgE, Fc epsilon RI, in the pathogenesis of primary EGIDs. Beyond its defined role in type I allergic reactions, we here hypothesize that activation of tetrameric Fc epsilon RI on mast cells and basophils as well as trimeric Fc epsilon RI on human eosinophils and antigen presenting cells in the gastrointestinal mucosa is critically involved in the pathology of EGIDs. We also discuss how IgE-independent triggering of Fc epsilon RI could be a mechanisms responsible for activation of the immune system in patients with EGID.