title: Esophageal functional impairments in experimental eosinophilic esophagitis.
abstract: 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.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, OH 45229, USA.
authors.forename: Parm
authors.initials: P
authors.lastname: Mavi
authors.forename: Priya
authors.initials: P
authors.lastname: Rajavelu
authors.forename: Madhavi
authors.initials: M
authors.lastname: Rayapudi
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Paul
authors.forename: Anil
authors.initials: A
authors.lastname: Mishra
mesh_terms: D000818:Animals; D018801:CD2 Antigens / Q000378:metabolism; D004195:Disease Models, Animal; D057765:Eosinophilic Esophagitis / Q000378:metabolism / Q000503:physiopathology*; D004804:Eosinophils / Q000502:physiology*; D015154:Esophageal Motility Disorders / Q000378:metabolism / Q000503:physiopathology*; D004947:Esophagus / Q000378:metabolism / Q000503:physiopathology*; D015848:Interleukin-5 / Q000378:metabolism; D051379:Mice
chemical_list: D018801:CD2 Antigens; D015848:Interleukin-5