title: Potential for improving therapy and defining new research targets in eosinophilic oesophagitis based on understanding of immunopathogenesis.
abstract: OBJECTIVE
  This review considers the potential for therapeutic advances in the management of eosinophilic oesophagitis (EoE) based on recently increased understanding of the pathophysiology of the disorder.
  
  
  METHODS
  This is a review of publications characterising mucosal changes and leucocyte recruitment patterns in human and experimental EoE.
  
  
  RESULTS
  EoE, although diagnosed by epithelial infiltration of eosinophils, is actually a transmural inflammation in which eosinophil recruitment occurs via the deeper layers. Penetration of eosinophils into the epithelium is variable, explaining the need for multiple biopsies to diagnose what may be a clearly visible disorder. Fibrosis and neuromuscular dysfunction both occur within the subepithelial tissues. Recent murine studies have identified that T-cell recruitment underpins antigen-specific oesophageal eosinophil recruitment. Involvement of innate immunity is also suggested by the role of invariant natural killer T cells in experimental EoE.
  
  
  CONCLUSIONS
  Looking beyond present therapeutic options with a view to future studies, we identify T cells as candidates for "upstream therapy" if antigen specificity or homing markers are determined. Evidence of aeroallergen sensitisation suggests the possibility of lymphocyte priming within nasal-associated lymphoid tissue or Waldeyer ring, with the potential for topical therapy. We consider acquired neuromuscular dysfunction as a therapeutic target in acute symptomatic deterioration or bolus obstruction. We assess possible similarities with therapeutic stratagems for chronic asthma, recognising at the same time the anatomic specificity of the oesophagus and the difficulty in delivering effective topical medication to subepithelial tissues in this location compared with the airway.
authors.affiliation: *Division of Metabolic and Vascular Health, Warwick Medical School, Coventry, UK †Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia ‡Department of Paediatrics, St Mary's Hospital for Children, Carshalton, UK §Department of Paediatrics, Hospital St João, Porto, Portugal ||Department of Paediatrics, Athens Children's Hospital, Athens, Greece.
authors.forename: Simon H
authors.initials: SH
authors.lastname: Murch
authors.forename: Katrina
authors.initials: K
authors.lastname: Allen
authors.forename: Sonny
authors.initials: S
authors.lastname: Chong
authors.forename: Jorge Amil
authors.initials: JA
authors.lastname: Dias
authors.forename: Alexandra
authors.initials: A
authors.lastname: Papadopoulou
mesh_terms: D000818:Animals; D057765:Eosinophilic Esophagitis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004804:Eosinophils / Q000473:pathology*; D004947:Esophagus / Q000276:immunology / Q000473:pathology; D006801:Humans; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D009468:Neuromuscular Diseases / Q000209:etiology; D013601:T-Lymphocytes