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

Abstract

BackgroundThe role of the high affinity IgE receptor, FcεRI, in IgE-mediated immune responses of the gastrointestinal (GI) mucosa is poorly understood. Currently, a detailed characterization of FcεRI expression throughout the human gut is lacking. The aim of this study was to define the expression pattern of FcεRI in the GI tract.Methods/Principal FindingsWe compared FcεRI expression in children with gastritis/esophagitis (n = 10), celiac disease (n = 10), inflammatory bowel disease (IBD) (n = 9), and normal mucosa (n = 5). The α–subunit of FcεRI (FcεRIα), 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 FcεRIα and -β expression levels decreased towards the distal intestine. mRNA transcripts of the common Fc-receptor-γ chain were present in the entire GI mucosa. Double-immunofluorescence staining of esophageal specimens confirmed that FcεRIα was expressed on intraepithelial mast cells and Langerhans cells. The mRNA expression levels of the α, β, and γ subunits of FcεRI did not correlate with total serum IgE but were associated with mucosal inflammation.Conclusion/SignificanceOur data define the upper GI tract as the main site for IgE-mediated immune activation via FcεRI. Tissue mRNA levels of FcεRIα are regulated by inflammatory conditions rather than serum IgE, indicating that FcεRI might also play a role in pathologies other than allergy.

Accumulation of BDCA1+ Dendritic Cells in Interstitial Fibrotic Lung Diseases and Th2-High Asthma

“…However, the extent to which FcεRI is expressed in a more comprehensive lung DC subset has not been examined. Our study indicates that FcεRI is constitutively expressed in BDCA1 + lung DCs, similarly to what had been found in blood, tonsil [22], and intestine [44]. Furthermore, a recent study revealed that FcεRI is expressed in BDCA1 + DCs in human arthritic synovial fluid and malignant tumor ascites [15], and additionally demonstrated that FcεRI is a useful marker that distinguishes DCs from macrophages, which do not express FcεRI but do express mannose receptors and DC-SIGN [15].…”

Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction

“…These novel data, along with increased awareness of potential linkbetween asthma (where HDM is clearly implicated) and IBD,37 it is tempting to speculate a central role of HDM in the link between these two diseases. In addition, we can envisage that HDM effect may be potentiated in inflammatory conditions where lower GIT becomes susceptible to IgE-mediated responses 38 39. Indeed, in this paper, we have shown HDM to further increase epithelial permeability in patients with IBS.…”

Allergic Mechanisms in Eosinophilic Esophagitis

“…45 This may be due histopathologic variability or may represent a key etiologic difference between children and adults with EoE. Additionally, Langerhans cells of the upper GI tract express the high-affinity IgE receptor, FcεRI, 46 for which expression increases in active EoE. 47 IgE signaling on APCs has been proposed to enhance antigen uptake and enhance the development and activation of allergen-specific T-cells.…”