title: Role of IL-17A and neutrophils in fibrosis in experimental hypersensitivity pneumonitis.
abstract: BACKGROUND
  Chronic hypersensitivity pneumonitis is characterized by pulmonary inflammation and fibrosis in response to repeated inhalation of mainly organic antigens. It is recognized that IL-17A is crucial for the development of pulmonary inflammation in murine models of experimental hypersensitivity pneumonitis, but its role in the development of pulmonary fibrosis has not been determined. Furthermore, the main cell type(s) that produce IL-17A in experimental hypersensitivity pneumonitis have not yet been identified.
  
  
  OBJECTIVE
  Our objectives were to test the hypothesis that IL-17A plays a central role in the development of pulmonary fibrosis in experimental hypersensitivity pneumonitis and to determine the main inflammatory cell type(s) responsible for IL-17A production.
  
  
  METHODS
  We used a mouse model of experimental hypersensitivity pneumonitis in which IL-17A was inhibited or neutrophils were depleted. We also used IL-17RA-deficient and RAG-2-deficient mice. Lung IL-17A-producing cells were identified by fluorescence-activated cell sorting of myeloid versus lymphoid cell populations, intracellular IL-17A staining, flow cytometry, and quantitative reverse transcription PCR for IL-17A mRNA.
  
  
  RESULTS
  We found that the development of pulmonary fibrosis depended on IL-17A and was significantly attenuated by neutrophil depletion. Neutrophils and monocytes/macrophages were the main cell types that expressed IL-17A in our model.
  
  
  CONCLUSIONS
  We have identified the central roles of IL-17A and neutrophils in the pathogenesis of fibrosis in experimental hypersensitivity pneumonitis. We have also established that nonlymphocytic innate immune cells, specifically neutrophils and monocytes/macrophages, rather than TH17 lymphocytes, are the predominant source of IL-17A in experimental hypersensitivity pneumonitis.
authors: Airway Inflammation Research Group, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
authors: Simon A
authors: SA
authors: Hasan
authors: Bertus
authors: B
authors: Eksteen
authors: Danielle
authors: D
authors: Reid
authors: Heather V
authors: HV
authors: Paine
authors: Abrar
authors: A
authors: Alansary
authors: Kerri
authors: K
authors: Johannson
authors: Carol
authors: C
authors: Gwozd
authors: Kimberly-Ann R
authors: KA
authors: Goring
authors: Tina
authors: T
authors: Vo
authors: David
authors: D
authors: Proud
authors: Margaret M
authors: MM
authors: Kelly
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002630:Chemotactic Factors / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology*; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D016930:Saccharopolyspora / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D002630:Chemotactic Factors; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D053773:Transforming Growth Factor beta1