title: 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.
  
  
  METHODS
  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.affiliation: Section of Pediatric Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, , Aurora, Colorado, USA.
authors.forename: Joanne C
authors.initials: JC
authors.lastname: Masterson
authors.forename: Eóin N
authors.initials: EN
authors.lastname: McNamee
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hosford
authors.forename: Kelley E
authors.initials: KE
authors.lastname: Capocelli
authors.forename: Joseph
authors.initials: J
authors.lastname: Ruybal
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Fillon
authors.forename: Alfred D
authors.initials: AD
authors.lastname: Doyle
authors.forename: Holger K
authors.initials: HK
authors.lastname: Eltzschig
authors.forename: Anil K
authors.initials: AK
authors.lastname: Rustgi
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Protheroe
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Lee
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Glenn T
authors.initials: GT
authors.lastname: Furuta
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D057765:Eosinophilic Esophagitis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D004848:Epithelium; D004854:Herpesvirus 4, Human; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010081:Oxazolone; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D015848:Interleukin-5; D054334:Viral Regulatory and Accessory Proteins; D010081:Oxazolone; D003907:Dexamethasone