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Interleukin-17-mediated immunopathogenesis in experimental hypersensitivity pneumonitis.

Authors: Joshi, AD  Fong, DJ  Oak, SR  Trujillo, G  Flaherty, KR  Martinez, FJ  Hogaboam, CM 
Citation: Joshi AD, etal., Am J Respir Crit Care Med. 2009 Apr 15;179(8):705-16. Epub 2009 Jan 16.
Pubmed: (View Article at PubMed) PMID:19151189
DOI: Full-text: DOI:10.1164/rccm.200811-1700OC

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.


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CRRD Object Information
CRRD ID: 4889106
Created: 2010-11-24
Species: All species
Last Modified: 2010-11-24
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.