title: Invited lecture: activation of the epithelial mesenchymal trophic unit in the pathogenesis of asthma.
abstract: BACKGROUND
  A recent NIH Workshop and an ERS Task Force concluded that more work was needed to understand mechanisms of severe and chronic asthma. This report describes a series of studies that identify aberrant epithelial mesenchymal signalling in the airways as an important event in maintaining inflammation and driving remodelling in response to environmental injury.
  
  
  METHODS
  Immunohistochemistry, genotyping and functional studies conducted on cultured asthmatic cells and mucosal biopsies were used to identify biochemical pathways involved in epithelial injury and repair in asthma and their relationship to disease severity.
  
  
  RESULTS
  Our findings suggest that the asthmatic state results from an interaction between a susceptible epithelium and Th-2-mediated inflammation to alter the communication between the epithelium and the underlying mesenchyme - the epithelial mesenchymal trophic unit - leading to disease persistence, airway remodelling and refractoriness to corticosteroid treatment.
  
  
  CONCLUSIONS
  Asthma is more than an inflammatory disorder, but requires engagement of important signalling pathways involved in epithelial repair and tissue remodelling. These pathways involving EGFRs and TGF-betaRs provide targets against which to develop novel therapies for chronic asthma.
authors: Respiratory Cell and Molecular Biology Division, School of Medicine, Southampton General Hospital, Southampton, UK. sth@soton.ac.uk
authors: S T
authors: ST
authors: Holgate
authors: P M
authors: PM
authors: Lackie
authors: P H
authors: PH
authors: Howarth
authors: W R
authors: WR
authors: Roche
authors: S M
authors: SM
authors: Puddicombe
authors: A
authors: A
authors: Richter
authors: S J
authors: SJ
authors: Wilson
authors: J W
authors: JW
authors: Holloway
authors: D E
authors: DE
authors: Davies
mesh_terms: D001249:Asthma / Q000235:genetics / Q000276:immunology*; D002908:Chronic Disease; D016207:Cytokines / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D053661:Interleukin-13 Receptor alpha1 Subunit; D019899:Paracrine Communication; D011110:Polymorphism, Genetic; D018123:Receptors, Interleukin / Q000235:genetics; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D020545:Respiratory Mucosa / Q000276:immunology*; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; C508181:IL13RA1 protein, human; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D018125:Receptors, Transforming Growth Factor beta; D066246:ErbB Receptors