Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis. Issue 1 (17th November 2012)

• Record Type: Journal Article
• Authors: Masterson, Joanne C; McNamee, Eóin N; Hosford, Lindsay; Capocelli, Kelley E; Ruybal, Joseph; Fillon, Sophie A; Doyle, Alfred D; Eltzschig, Holger K; Rustgi, Anil K; Protheroe, Cheryl A; Lee, Nancy A; Lee, James J; Furuta, Glenn T
• Is Part Of: Gut. Volume 63:Issue 1(2014)
• Page Start: 43
• Page End: 53
• Publication Date: 2012-11-17
• Subjects: Mucosal Pathology -- Food Allergy -- Oesophageal Disease -- Oesophagitis -- Paediatric Gastroenterology; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2012-303631
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Objective: Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition of the oesophagus with limited treatment options. No previous transgenic model has specifically targeted the oesophageal mucosa to induce oesophageal eosinophilia. Design: We developed a mouse model that closely resembles EoE by utilising oxazolone haptenation in mice with transgenic overexpression of an eosinophil poietic and survival factor (interleukin (IL)-5) in resident squamous oesophageal epithelia. Results: Overexpression of IL-5 in the healthy oesophagus was achieved in transgenic mice ( L2-IL5 ) using the squamous epithelial promoter Epstein–Barr virus ED-L2. Oxazolone-challenged L2-IL5 mice developed dose-dependent pan-oesophageal eosinophilia, including eosinophil microabscess formation and degranulation as well as basal cell hyperplasia. Moreover, oesophagi expressed increased IL-13 and the eosinophil agonist chemokine eotaxin-1. Treatment of these mice with corticosteroids significantly reduced eosinophilia and epithelial inflammation. Conclusions: L2-IL5 mice provide a novel experimental model that can potentially be used in preclinical testing of EoE-related therapeutics and mechanistic studies identifying pathogenetic features associated with mucosal eosinophilia.