Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span

Little is known about the relative importance of monocyte and tissue-resident macrophages in the development of lung fibrosis. We show that specific genetic deletion of monocyte-derived alveolar macrophages after their recruitment to the lung ameliorated lung fibrosis, whereas tissue-resident alveolar macrophages did not contribute to fibrosis. Using transcriptomic profiling of flow-sorted cells, we found that monocyte to alveolar macrophage differentiation unfolds continuously over the course of fibrosis and its resolution. During the fibrotic phase, monocyte-derived alveolar macrophages differ significantly from tissue-resident alveolar macrophages in their expression of profibrotic genes. A population of…

• UD
  U.S. Department of Defense

  Award: PR141319
• AT
  American Thoracic Society
• SF
  Scleroderma Foundation
• SO
  Society of University Surgeons Foundation
• AA
  American Association for Thoracic Surgery
• NU
  Northwestern University

  Award: 5T32 HL076139-13
• TS
  Thoracic Surgery Foundation
• BB
  BD Biosciences
• NI
  National Institutes of Health

  Awards: AR064313, AR064546, ES025644, HL124664, HL128867, AG049665, HL134375, HL071643, T32 DK077662, HL125940, HL079190, HL085534, HL048129, ES013995, ES015024
• FS
  Feinberg School of Medicine
• NC
  National Cancer Institute

  Award: P30 CA060553
• NI
  National Institute of Arthritis and Musculoskeletal and Skin Diseases

  Award: AR061593