title: Interleukin-17-mediated immunopathogenesis in experimental hypersensitivity pneumonitis.
abstract: BACKGROUND
  T cells play a critical role in the development of Saccharopolyspora rectivirgula-induced hypersensitivity pneumonitis (HP) but little is known about the role of IL-17A in this disease.
  
  
  OBJECTIVE
  We examined the role of IL-17A in a murine model of S. rectivirgula antigen (SR-Ag)-induced HP.
  
  
  METHODS
  Experimental HP was induced by oropharyngeal instillation of SR-Ag in wild-type and IL-17 gene-deficient mice.
  
  
  RESULTS
  SR-Ag-induced murine HP was characterized by increased transcript levels of IFN-gamma and IL-12p35 compared with saline-treated control mice. Furthermore, mice with HP showed increased IL-17 in lung homogenates, bronchoalveolar lavage fluid, and ex-vivo lung cultures compared with control mice. Flow cytometric analysis of SR-Ag-challenged lungs revealed increased Th17 and CD11c(+) cells. The role of IL-17 in SR-induced HP was examined in IL-17 deficient (IL17(-/-)) and in wild-type (IL-17(+/+)) mice immunodepleted of IL-17. Histological examination of IL17(-/-) mice challenged with SR-Ag revealed reduced inflammatory cell infiltration, decreased CD11c(+) cells, and reduced levels of inflammatory mediators such as IL-12p70, CCL3, and CXCL9 compared with similarly treated IL17(+/+) mice. Anti-IL-17 antibody treatment of IL-17(+/+) mice with HP resulted in reduced inflammation and a lower percentage of CD11c(+) cells compared with IgG-treated IL-17(+/+) mice with HP.
  
  
  CONCLUSIONS
  SR-Ag-induced IL-17 plays a pivotal role in the immunopathology of HP and targeting IL-17 is an attractive therapeutic option for this disease.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
authors.forename: Amrita D
authors.initials: AD
authors.lastname: Joshi
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fong
authors.forename: Sameer R
authors.initials: SR
authors.lastname: Oak
authors.forename: Glenda
authors.initials: G
authors.lastname: Trujillo
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Flaherty
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: Cory M
authors.initials: CM
authors.lastname: Hogaboam
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016930:Saccharopolyspora / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D015703:Antigens, CD; D020381:Interleukin-17