[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Yanagisawa, Haruhiko
Hashimoto, Mitsuo
Minagawa, Shunsuke
Takasaka, Naoki
Ma, Royce
MOERMANS, Catherine ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Clinique de l'asthme
Ito, Saburo
Araya, Jun
Budelsky, Alison
Goodsell, Amanda
Baron, Jody L.
Nishimura, Stephen L.
Language :
English
Title :
Role of IL-17A in murine models of COPD airway disease.
Publication date :
2017
Journal title :
American Journal of Physiology - Lung Cellular and Molecular Physiology
ISSN :
1040-0605
eISSN :
1522-1504
Publisher :
American Physiological Society, United States - Maryland
Volume :
312
Issue :
1
Pages :
L122-L130
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2017 the American Physiological Society.
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