Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis

JC Masterson, EN McNamee, L Hosford, KE Capocelli… - Gut, 2014 - gut.bmj.com
JC Masterson, EN McNamee, L Hosford, KE Capocelli, J Ruybal, SA Fillon, AD Doyle
Gut, 2014gut.bmj.com
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 …
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.
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