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. Currently there are limited effective therapeutics for pulmonary fibrosis due to an inadequate understanding of the pathogenic process and underlying mechanisms. We now show that in human idiopathic pulmonary fibrosis (IPF) the cytokine interleukin (IL)-25 positively correlates with periostin a marker human pulmonary fibrosis, and the presence of IL-13-producing type 2 innate lymphoid cells (ILC2) in the lung. Using murine models of pulmonary fibrosis we demonstrate an essential role for IL-25-elicited ILC2 in the generation of pulmonary collagen deposition, independent of an adaptive T cell response. Furthermore, we define a mechanism whereby IL-25 evokes ILC2 to induce pulmonary fibrosis via the alternative activation of macrophages in the lung. Collectively, we present a new 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 indicate that IL-25 and ILC2 are potential therapeutic targets for the treatment of human fibrotic diseases where antigen-independent damage responses may magnify the disease.
- Copyright © 2013 by The American Association of Immunologists, Inc.