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Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):367-72. doi: 10.1073/pnas.1315854111. Epub 2013 Dec 16.

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

Author information

1
Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin 2, Ireland.

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.

KEYWORDS:

cytokine; inflammation; innate response; therapy

PMID:
24344271
PMCID:
PMC3890791
DOI:
10.1073/pnas.1315854111
[Indexed for MEDLINE]
Free PMC Article

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