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Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis
  1. Joanne C Masterson1,2,3,4,5,
  2. Eóin N McNamee4,5,6,
  3. Lindsay Hosford1,2,3,4,5,
  4. Kelley E Capocelli2,3,5,7,
  5. Joseph Ruybal1,2,3,4,5,
  6. Sophie A Fillon1,2,3,4,5,
  7. Alfred D Doyle8,
  8. Holger K Eltzschig4,5,6,
  9. Anil K Rustgi9,
  10. Cheryl A Protheroe8,
  11. Nancy A Lee8,
  12. James J Lee8,
  13. Glenn T Furuta1,2,3,4,5
  1. 1Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Aurora, Colorado, USA
  2. 2Gastrointestinal Eosinophilic Diseases Program, Aurora, Colorado, USA
  3. 3Children's Hospital Colorado, Aurora, Colorado, USA
  4. 4Mucosal Inflammation Program, University of Colorado Denver, Aurora, Colorado, USA
  5. 5University of Colorado Denver School of Medicine, Aurora, Colorado, USA
  6. 6Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado, USA
  7. 7Department of Pathology, Children's Hospital Colorado, Aurora, Colorado, USA
  8. 8Department of Biochemistry and Molecular Biology, Mayo Clinic Scottsdale, Arizona, USA
  9. 9Division of Gastroenterology, Department of Medicine and Genetics, University of Pennsylvania, Philadelphia, USA
  1. Correspondence to Dr Glenn T Furuta, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, 13123 East 16th Avenue, B290, Aurora, CO 80045, USA; glenn.furuta{at}childrenscolorado.org

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.

  • Mucosal Pathology
  • Food Allergy
  • Oesophageal Disease
  • Oesophagitis
  • Paediatric Gastroenterology

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