title: Interleukin-17 signalling in a murine model of mild chronic asthma.
abstract: BACKGROUND
  The role of Th17 cell-derived cytokines in the pathogenesis of airway inflammation and remodelling in mild asthma remains unclear. We investigated this in a mouse model which reproduces most of the features of the human disease.
  
  
  METHODS
  Systemically sensitised BALB/c mice were challenged via the airways with a low mass concentration of ovalbumin aerosol for 8 weeks to induce lesions of mild chronic asthma. Changes were compared with those in animals deficient in signalling via the interleukin (IL)-17 receptor A (IL-17R). Low-passage airway epithelial cells (AEC) and fibroblasts were cultured with IL-17A, or with media from Th17-polarised cells, to assess activation.
  
  
  RESULTS
  In CD4+ T cells from chronically challenged mice, expression of mRNA for Th17 cytokines IL-17A, IL-17F, IL-21 and IL-22 was significantly increased. Both recombinant IL-17A and media from Th17 cells significantly stimulated the production of various pro-inflammatory and pro-remodelling cytokines by AEC and fibroblasts. In the mouse model, abrogation of IL-17R signalling had no effect on the development of airway inflammation or on most changes of remodelling. However, numbers of mucus-producing cells and expression of mRNA for Gob-5 were attenuated in the absence of IL-17R signalling.
  
  
  CONCLUSIONS
  Although IL-17A and Th17 cells stimulate cytokine production by structural cells of the airways, and Th17 cells are induced in our model of mild chronic asthma, signalling via IL-17R did not contribute significantly to the development of airway inflammation and most changes of remodelling in this model. However, in mild asthma, IL-17A appears to have a role in the goblet cell response in the airways.
authors.affiliation: Inflammation and Infection Research, Department of Pathology, School of Medical Sciences, University of New South Wales, Sydney, N.S.W., Australia.
authors.forename: Cristan
authors.initials: C
authors.lastname: Herbert
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Shadie
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Kumar
mesh_terms: D056151:Airway Remodeling / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D053722:Receptors, Interleukin-17