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IL- 25 and type 2 innate lymphoid cells induce pulmonary fibrosis

Hams, Emily, Armstrong, Michelle E., Barlow, Jillian L., Saunders, Sean P., Schwartz, Christian, Cooke, Gordon, Fahy, Ruairi J., Crotty, Thomas B., Hirani, Nikhil, Flynn, Robin J., Voehringer, David, McKenzie, Andrew N. J., Donnelly, Seamas C., Fallon, Padraic G.
Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.1 pp. 367-372
animal models, collagen, complications (disease), fibrosis, humans, immune response, interleukin-13, lungs, mice, morbidity, mortality, patients, prognosis
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.