Interleukin-17-mediated immunopathogenesis in experimental hypersensitivity pneumonitis.
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.
Joshi
Amrita D
AD
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Fong
Daniel J
DJ
Oak
Sameer R
SR
Trujillo
Glenda
G
Flaherty
Kevin R
KR
Martinez
Fernando J
FJ
Hogaboam
Cory M
CM
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
D000942:Antigens, Bacterial; D015703:Antigens, CD; D020381:Interleukin-17