IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis.
Item Type:Journal Article
Citation:Hams E, Armstrong ME, Barlow JL, Saunders SP, Schwartz C, Cooke G, Fahy RJ, Crotty TB, Hirani N, Flynn RJ, Voehringer D, McKenzie AN, Donnelly SC, Fallon PG, IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis., Proceedings of the National Academy of Sciences of the United States of America, 111, 1, 2014, 367-72
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Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Using murine models we demonstrate a role for interleukin (IL)-25 in the generation of pulmonary fibrosis. Mechanistically, we identify IL-13 release from type 2 innate lymphoid cells (ILC2) as sufficient to drive collagen deposition in the lungs of challenged mice and suggest this as a potential mechanism through which IL-25 is acting. Additionally, we demonstrate that in human idiopathic pulmonary fibrosis there is increased pulmonary expression of IL-25 and also observe a population ILC2 in the lungs of idiopathic pulmonary fibrosis patients. Collectively, we present an innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2, that occurs independently of T-cell-mediated antigen-specific immune responses. These results suggest the potential of therapeutically targeting IL-25 and ILC2 for the treatment of human fibrotic diseases.
Type of material:Journal Article
Series/Report no:Proceedings of the National Academy of Sciences of the United States of America
Availability:Full text available