Pathogenic role of mast cells in experimental eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is a chronic allergic disease characterized by esophageal intraepithelial eosinophils, extracellular eosinophil granule deposition, induced mast cell accumulation, and epithelial cell hyperplasia. However, the processes involved in the development of a number of these characteristics are largely unknown. Herein, we tested the hypothesis whether induced mast cell accumulation in the esophagus has a role in promoting EoE pathogenesis. Accordingly, we induced experimental EoE in wild-type mice, mast cell-deficient WWv mice, and mast cell-reconstituted WWv mice. We report that esophageal mast cell numbers increase in parallel with eosinophils in a dose- and time-dependent manner following the induction of allergen-induced EoE. The induced mast cells are localized in the esophageal lamina propria and muscular mucosa but have no influence on promoting esophageal eosinophilia. The 5'-bromodeoxyuridine (BrdU) incorporation analysis indicated that mast cells have a significant role in muscle cell hyperplasia and hypertrophy. In addition, the wild-type and mast cell-reconstituted WWv mice showed a comparable number of BrdU⁺ cells in the esophageal muscular mucosa following allergen-induced EoE. In conclusion, we provide for the first time direct evidence that mast cell promotes muscle cell hyperplasia and hypertrophy and may have a significant role in promoting esophageal functional abnormalities in EoE.