Dietary treatment modulates mast cell phenotype, density, and activity in adult eosinophilic oesophagitis

Background Mast cells (MCs) are abundant in the inflammatory infiltrate in eosinophilic esophagitis (EoE), but decrease with disease remission. However, their phenotype, role in the pathophysiology of the disease, and modulation after effective dietary therapy are still unclear. Objective To define the phenotype of esophageal MCs, their modulation through dietary therapy, and their association with clinical manifestations of EoE. Methods Esophageal mucosal samples from 10 adult EoE patients obtained before and after effective six-food elimination diet (SFED) therapy, as well as from 10 control subjects were analyzed. Eosinophil and MC density were quantified. Gene expression of chemoattractants for eosinophils (CCL11, CCL24, and CCL26), MCs (SCF), and their receptors (CCR3 and SCFR, respectively) were assessed by means of qPCR. Gene and protein expression of specific MC proteases (CPA3, CMA, and TPSB2) were evaluated with qPCR and immunofluorescence. Clinical manifestations and atopic background were recorded. Results MC density was significantly increased in EoE compared to controls, decreasing after dietary treatment (18.6 to 1.44 cells/hpf, respectively; p<0.001). The MCTC subtype predominated in the esophageal mucosa (90%) in both EoE patients and controls. Gene expression of MC-related proteases, eotaxins, and SCF were upregulated in EoE patients, but significantly decreased after therapy, regardless of atopic background. Epithelial peaks of MCs and eosinophils were significantly associated (rho=0.80) in EoE and correlated with the symptom score (rho=0.78). Gene expression of MC proteases and eotaxins also correlated with the symptom score (p<0.05). Conclusions MC and its proteases seem to play a relevant role in the pathophysiology and symptoms of EoE, which can be reversed after effective dietary treatment. This article is protected by copyright. All rights reserved.