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, Seamus C.; Fallon, Padraic G.

Abstract

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.

Citation

Hams, E., Armstrong, M. E., Barlow, J. L., Saunders, S. P., Schwartz, C., Cooke, G., …Fallon, P. G. (2014). IL-25 and type 2 innate lymphoid cells induce pulmonary fibrosis. Proceedings of the National Academy of Sciences, 111(1), 367-372. https://doi.org/10.1073/pnas.1315854111

• Journal Article Type: Article
• Acceptance Date: Nov 15, 2013
• Online Publication Date: Dec 16, 2013
• Publication Date: Jan 7, 2014
• Deposit Date: Sep 29, 2020
• Journal: Proceedings of the National Academy of Sciences
• Print ISSN: 0027-8424
• Electronic ISSN: 1091-6490
• Publisher: National Academy of Sciences
• Peer Reviewed: Peer Reviewed
• Volume: 111
• Issue: 1
• Pages: 367-372
• DOI: https://doi.org/10.1073/pnas.1315854111
• Keywords: Multidisciplinary
• Public URL: https://nottingham-repository.worktribe.com/output/3897486
• Publisher URL: https://www.pnas.org/content/111/1/367