PT  - JOURNAL ARTICLE
AU  - Joanne C Masterson
AU  - Eóin N McNamee
AU  - Lindsay Hosford
AU  - Kelley E Capocelli
AU  - Joseph Ruybal
AU  - Sophie A Fillon
AU  - Alfred D Doyle
AU  - Holger K Eltzschig
AU  - Anil K Rustgi
AU  - Cheryl A Protheroe
AU  - Nancy A Lee
AU  - James J Lee
AU  - Glenn T Furuta
TI  - Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis
AID  - 10.1136/gutjnl-2012-303631
DP  - 2014 Jan 01
TA  - Gut
PG  - 43--53
VI  - 63
IP  - 1
4099  - http://gut.bmj.com/content/63/1/43.short
4100  - http://gut.bmj.com/content/63/1/43.full
SO  - Gut2014 Jan 01; 63
AB  - 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.