RGD Reference Report - Interleukin-17-mediated immunopathogenesis in experimental hypersensitivity pneumonitis. - Rat Genome Database

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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.
RGD ID: 4889106
Pubmed: PMID:19151189   (View Abstract at PubMed)
DOI: DOI:10.1164/rccm.200811-1700OC   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extrinsic allergic alveolitis  ISOIl17a (Mus musculus)4889106; 4889106 RGD 
extrinsic allergic alveolitis  ISOIl5 (Mus musculus)4889106; 4889106protein:increased expression:lung and respiratory system fluid/secretionRGD 
extrinsic allergic alveolitis  IMP 4889106 RGD 
extrinsic allergic alveolitis  IEP 4889106protein:increased expression:lung and respiratory system fluid/secretionRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il17a  (interleukin 17A)
Il5  (interleukin 5)

Genes (Mus musculus)
Il17a  (interleukin 17A)
Il5  (interleukin 5)

Genes (Homo sapiens)
IL17A  (interleukin 17A)
IL5  (interleukin 5)


Additional Information