| First Author | Yanagisawa H | Year | 2017 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 312 |
| Issue | 1 | Pages | L122-L130 |
| PubMed ID | 27913421 | Mgi Jnum | J:238719 |
| Mgi Id | MGI:5823510 | Doi | 10.1152/ajplung.00301.2016 |
| Citation | Yanagisawa H, et al. (2017) Role of IL-17A in murine models of COPD airway disease. Am J Physiol Lung Cell Mol Physiol 312(1):L122-L130 |
| abstractText | 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 alpha/beta 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 gammadelta 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. |
