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

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.

• Authors: Joanne C Masterson, Eóin 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
• Journal: Gut (Gut) Vol. 63 Issue 1 Pg. 43-53 (Jan 2014) ISSN: 1468-3288 [Electronic] England
• PMID: 23161496 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Biomarkers
• Interleukin-5
• Viral Regulatory and Accessory Proteins
• Oxazolone
• Dexamethasone

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Biomarkers (metabolism)
• Dexamethasone (therapeutic use)
• Disease Models, Animal
• Eosinophilic Esophagitis (drug therapy, etiology, metabolism)
• Epithelium
• Herpesvirus 4, Human
• Interleukin-5 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic (genetics, immunology, metabolism)
• Oxazolone
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Up-Regulation
• Viral Regulatory and Accessory Proteins