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Mediators of Inflammation
Volume 2018, Article ID 7934362, 15 pages
Research Article

TRAIL-Dependent Resolution of Pulmonary Fibrosis

1Women’s Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
2Immunology Group, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48103, USA
3Urologic Oncology Program and Uro-Oncology Research Laboratories, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
4Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit, Vrije Universiteit Medisch Centrum, 1081 BT Amsterdam, Netherlands

Correspondence should be addressed to David M. Habiel; gro.shsc@leibah.divad and Cory M. Hogaboam; gro.shsc@maobagoh.yroc

Received 7 August 2017; Accepted 2 November 2017; Published 24 January 2018

Academic Editor: Ruchi Bansal

Copyright © 2018 David M. Habiel et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Idiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease characterized by the persistence of activated myofibroblasts resulting in excessive deposition of extracellular matrix proteins and profound tissue remodeling. In the present study, the expression of tumor necrosis factor- (TNF-) related apoptosis-inducing ligand (TRAIL) was key to the resolution of bleomycin-induced pulmonary fibrosis. Both in vivo and in vitro studies demonstrated that Gr-1+TRAIL+ bone marrow-derived myeloid cells blocked the activation of lung myofibroblasts. Although soluble TRAIL was increased in plasma from IPF patients, the presence of TRAIL+ myeloid cells was markedly reduced in IPF lung biopsies, and primary lung fibroblasts from this patient group expressed little of the TRAIL receptor-2 (DR5) when compared with appropriate normal samples. IL-13 was a potent inhibitor of DR5 expression in normal fibroblasts. Together, these results identified TRAIL+ myeloid cells as a critical mechanism in the resolution of pulmonary fibrosis, and strategies directed at promoting its function might have therapeutic potential in IPF.