Reference : Role of IL-17A in murine models of COPD airway disease.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Role of IL-17A in murine models of COPD airway disease.
Yanagisawa, Haruhiko [> >]
Hashimoto, Mitsuo [> >]
Minagawa, Shunsuke [> >]
Takasaka, Naoki [> >]
Ma, Royce [> >]
MOERMANS, Catherine mailto [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. [> >]
American Journal of Physiology - Lung Cellular and Molecular Physiology
Yes (verified by ORBi)
United States
[en] Adenoviridae/metabolism ; Animals ; Disease Models, Animal ; Interleukin-17/metabolism ; Interleukin-1beta/pharmacology ; Mice, Inbred C57BL ; Neutralization Tests ; Pneumonia/complications/metabolism/pathology ; Poly I-C/pharmacology ; Pulmonary Disease, Chronic Obstructive/complications/metabolism/pathology ; Pulmonary Fibrosis/complications/metabolism/pathology ; Receptors, Interleukin-17/metabolism ; Smoking/adverse effects ; airway ; cigarette smoke ; fibrosis ; inflammation ; interleukin-17
[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.
Copyright (c) 2017 the American Physiological Society.

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