Local Hypersensitivity Reaction in Transgenic Mice with Squamous Epithelial IL-5 Overexpression Provides a Novel Model of Eosinophilic Oesophagitis

Overview

Journal Gut

Specialty Gastroenterology

Date 2012 Nov 20

PMID 23161496

Citations 34

Authors

Joanne C Masterson

Eoin N McNamee

Lindsay Hosford

Kelley E Capocelli

Joseph Ruybal

Sophie A Fillon

Alfred D Doyle

Holger K Eltzschig

Anil K Rustgi

Cheryl A Protheroe

Nancy A Lee

James J Lee

Glenn T Furuta

Affiliations

Soon will be listed here.

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.

Citing Articles

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