Fc-Epsilon-RI, the High Affinity IgE-Receptor, Is Robustly Expressed in the Upper Gastrointestinal Tract and Modulated by Mucosal Inflammation

Background: The role of the high affinity IgE receptor, Fc epsilon RI, in IgE-mediated immune responses of the gastrointestinal (GI) mucosa is poorly understood. Currently, a detailed characterization of FceRI expression throughout the human gut is lacking. The aim of this study was to define the expression pattern of FceRI in the GI tract. Methods/Principal Findings: We compared FceRI expression in children with gastritis/esophagitis (n = 10), celiac disease (n = 10), inflammatory bowel disease (IBD) (n = 9), and normal mucosa (n = 5). The alpha-subunit of Fc epsilon RI (Fc epsilon RI alpha), detected by immunohistochemistry, was found on cells infiltrating the mucosa of the esophagus, the stomach, and the duodenum, but was rarely detected in more distal sections of the GI tract. Accordingly, quantitative RT-PCR analysis on esophagus, stomach, duodenum, colon, and rectum biopsies revealed that Fc epsilon RI alpha and -beta expression levels decreased towards the distal intestine. mRNA transcripts of the common Fc-receptor-gamma chain were present in the entire GI mucosa. Double-immunofluorescence staining of esophageal specimens confirmed that Fc epsilon RI alpha was expressed on intraepithelial mast cells and Langerhans cells. The mRNA expression levels of the alpha, beta, and gamma subunits of Fc epsilon RI did not correlate with total serum IgE but were associated with mucosal inflammation. Conclusion/Significance: Our data define the upper GI tract as the main site for IgE-mediated immune activation via Fc epsilon RI. Tissue mRNA levels of Fc epsilon RIa are regulated by inflammatory conditions rather than serum IgE, indicating that Fc epsilon RI might also play a role in pathologies other than allergy.