title: IL-25 drives remodelling in allergic airways disease induced by house dust mite.
abstract: BACKGROUND
  Overexpression of the transforming growth factor β family signalling molecule smad2 in the airway epithelium provokes enhanced allergen-induced airway remodelling in mice, concomitant with elevated levels of interleukin (IL)-25.
  
  
  OBJECTIVE
  We investigated whether IL-25 plays an active role in driving this airway remodelling.
  
  
  METHODS
  Anti-IL-25 antibody was given to mice exposed to either inhaled house dust mite (HDM) alone, or in conjunction with an adenoviral smad2 vector which promotes an enhanced remodelling phenotype.
  
  
  RESULTS
  Blocking IL-25 in allergen-exposed mice resulted in a moderate reduction in pulmonary eosinophilia and levels of T helper type 2 associated cytokines, IL-5 and IL-13. In addition, IL-25 neutralisation abrogated peribronchial collagen deposition, airway smooth muscle hyperplasia and airway hyperreactivity in control mice exposed to HDM and smad2-overexpressing mice. IL-25 was shown to act directly on human fibroblasts to induce collagen secretion. Recruitment of endothelial progenitor cells to the lung and subsequent neovascularisation was also IL-25 dependent, demonstrating a direct role for IL-25 during angiogenesis in vivo. Moreover, the secretion of innate epithelial derived cytokines IL-33 and thymic stromal lymphopoietin (TSLP) was completely ablated.
  
  
  CONCLUSIONS
  In addition to modulating acute inflammation, we now demonstrate a role for IL-25 in orchestrating airway remodelling. IL-25 also drives IL-33 and TSLP production in the lung. These data delineate a wider role for IL-25 in mediating structural changes to the lung following allergen exposure and implicate IL-25 as a novel therapeutic target for the treatment of airway remodelling in asthma.
authors.affiliation: Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Gregory
authors.forename: Carla P
authors.initials: CP
authors.lastname: Jones
authors.forename: Simone A
authors.initials: SA
authors.lastname: Walker
authors.forename: Devika
authors.initials: D
authors.lastname: Sawant
authors.forename: Kate H C
authors.initials: KH
authors.lastname: Gowers
authors.forename: Gaynor A
authors.initials: GA
authors.lastname: Campbell
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
authors.forename: Clare M
authors.initials: CM
authors.lastname: Lloyd
mesh_terms: D056151:Airway Remodeling / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D001707:Biopsy, Needle; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D039981:Pyroglyphidae / Q000276:immunology*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D051899:Smad2 Protein / Q000276:immunology
chemical_list: D007378:Interleukins; C442281:Mydgf protein, mouse; D051899:Smad2 Protein; C497783:Smad2 protein, mouse