Role of IL-17A in murine models of COPD airway disease
- 1 January 2017
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Lung Cellular and Molecular Physiology
- Vol. 312 (1), L122-L130
- https://doi.org/10.1152/ajplung.00301.2016
Abstract
Small airway fibrosis is a major pathological feature of chronic obstructive pulmonary disease (COPD) and is refractory to current treatments. Chronic inflammatory cells accumulate around small airways in COPD and are thought to play a major role in small airway fibrosis. Mice deficient in α/β T cells have recently been shown to be protected from both experimental airway inflammation and fibrosis. In these models, CD4+Th17 cells and secretion of IL-17A are increased. However, a pathogenic role for IL-17 in specifically mediating fibrosis around airways has not been demonstrated. Here a role for IL-17A in airway fibrosis was demonstrated using mice deficient in the IL-17 receptor A (il17ra). Il17ra-deficient mice were protected from both airway inflammation and fibrosis in two different models of airway fibrosis that employ COPD-relevant stimuli. In these models, CD4+ Th17 are a major source of IL-17A with other expressing cell types including γδ T cells, type 3 innate lymphoid cells, polymorphonuclear cells, and CD8+ T cells. Antibody neutralization of IL-17RA or IL-17A confirmed that IL-17A was the relevant pathogenic IL-17 isoform and IL-17RA was the relevant receptor in airway inflammation and fibrosis. These results demonstrate that the IL-17A/IL-17 RA axis is crucial to murine airway fibrosis. These findings suggest that IL-17 might be targeted to prevent the progression of airway fibrosis in COPD.Keywords
Funding Information
- HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI) (HL113032, HL063993, HL090662)
- HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) (NS044155)
- HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (P30DK026743)
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