Eosinophilic esophagitis (EoE) is an emerging chronic
esophageal disease. Despite the increasing diagnosis of EoE globally, the causes of EoE and other esophageal eosinophilic disorders are not clearly understood. EoE pathology includes accumulation of inflammatory cells (e.g., eosinophils, mast cells), characteristic endoscopic features (e.g., furrows, the formation of fine concentric mucosal rings, exudates), and functional impairments (e.g.,
esophageal stricture, dysmotility). We hypothesized that the esophageal structural pathology and functional impairments of EoE develop as a consequence of the effector functions of the accumulated inflammatory cells. We analyzed eosinophils (anti-major basic
protein immunostaining),
esophageal stricture (X-ray
barium swallowing), and esophageal motility (isometric force) in two established transgenic murine models of EoE (CD2-IL-5 and rtTA-CC10-IL-13) and a novel eosinophil-deficient model (ΔdblGATA/CD2-IL-5). Herein, we show the following: 1) CD2-IL-5 and
doxycycline (DOX)-induced rtTA-CC10-
IL-13 mice have chronic eosinophilic and mast cell esophageal
inflammation; 2) eosinophilic esophageal
inflammation promotes
esophageal stricture in both transgenic murine models; 3) the eosinophil-deficient ΔdblGATA/CD-2-IL-5 mice were protected from the induction of
stricture, whereas the eosinophil-competent CD2-IL-5 mice develop
esophageal stricture; 4)
esophageal stricture is not reversible in DOX-induced rtTA-CC10-
IL-13 mice (8 wk DOX followed by 8 wk no-DOX); and 5) IL-5 transgene-induced (CD2-IL-5) EoE evidences
esophageal dysmotility (relaxation and contraction) that is independent of the eosinophilic esophageal
inflammation: CD2-IL-5 and ΔdblGATA/CD2-IL-5 mice have comparable
esophageal dysmotility. Collectively, our present study directly implicates chronic eosinophilic
inflammation in the development of the esophageal structural impairments of experimental EoE.