Interleukin-17-mediated immunopathogenesis in experimental hypersensitivity pneumonitis

Am J Respir Crit Care Med. 2009 Apr 15;179(8):705-16. doi: 10.1164/rccm.200811-1700OC. Epub 2009 Jan 16.


Rationale: 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.

Objectives: 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.

Measurements and main 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolitis, Extrinsic Allergic / immunology*
  • Alveolitis, Extrinsic Allergic / microbiology
  • Animals
  • Antigens, Bacterial / immunology
  • Antigens, CD / immunology
  • Disease Models, Animal
  • Interleukin-17 / deficiency
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Saccharopolyspora / immunology
  • T-Lymphocytes / immunology


  • Antigens, Bacterial
  • Antigens, CD
  • Interleukin-17