Role of IL-17A and neutrophils in fibrosis in experimental hypersensitivity pneumonitis - 30/05/13
Abstract |
Background |
Chronic hypersensitivity pneumonitis is characterized by pulmonary inflammation and fibrosis in response to repeated inhalation of mainly organic antigens. It is recognized that IL-17A is crucial for the development of pulmonary inflammation in murine models of experimental hypersensitivity pneumonitis, but its role in the development of pulmonary fibrosis has not been determined. Furthermore, the main cell type(s) that produce IL-17A in experimental hypersensitivity pneumonitis have not yet been identified.
Objective |
Our objectives were to test the hypothesis that IL-17A plays a central role in the development of pulmonary fibrosis in experimental hypersensitivity pneumonitis and to determine the main inflammatory cell type(s) responsible for IL-17A production.
Methods |
We used a mouse model of experimental hypersensitivity pneumonitis in which IL-17A was inhibited or neutrophils were depleted. We also used IL-17RA–deficient and RAG-2–deficient mice. Lung IL-17A–producing cells were identified by fluorescence-activated cell sorting of myeloid versus lymphoid cell populations, intracellular IL-17A staining, flow cytometry, and quantitative reverse transcription PCR for IL-17A mRNA.
Results |
We found that the development of pulmonary fibrosis depended on IL-17A and was significantly attenuated by neutrophil depletion. Neutrophils and monocytes/macrophages were the main cell types that expressed IL-17A in our model.
Conclusions |
We have identified the central roles of IL-17A and neutrophils in the pathogenesis of fibrosis in experimental hypersensitivity pneumonitis. We have also established that nonlymphocytic innate immune cells, specifically neutrophils and monocytes/macrophages, rather than TH17 lymphocytes, are the predominant source of IL-17A in experimental hypersensitivity pneumonitis.
Le texte complet de cet article est disponible en PDF.Key words : Lung, interstitial lung disease, hypersensitivity pneumonitis, fibrosis, inflammation, IL-17A, neutrophils
Abbreviations used : BAL, BALT, EHP, FACS, HP, KC
Plan
Supported by grants from the Alberta Innovates - Health Solutions and the Lung Association of Alberta and the North West Territories. |
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Disclosure of potential conflict of interest: M. M. Kelly has received one or more grants from Alberta Innovates-Health Solutions and from the Alberta & NWT Lung Association. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 6
P. 1663 - juin 2013 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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