期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 214, 期 8, 页码 2387-2404出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20162152
关键词
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资金
- National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR061593]
- American Thoracic Society/Scleroderma Foundation research grant
- Department of Defense [PR141319]
- BD Bioscience immunology research grant
- Northwestern University's Lung Sciences Training Program [5T32 HL076139-13]
- NIH [AR064313, HL125940, HL128867, AG049665, HL048129, HL071643, HL085534, ES015024, ES025644, HL079190, HL124664, ES013995, AR064546, HL134375]
- Northwestern University's Transplant Surgery Scientist Training Program (NIH) [T32 DK077662]
- American Society for Transplant Surgery Foundation
- Thoracic Surgery Foundation
- Society of University Surgeons
- American Association of Thoracic Surgery John H. Gibbon Jr. Research Scholarship
- Parker B. Francis Research Opportunity Award
- Veterans Administration grant [BX000201]
- Mabel Greene Myers Chair
- National Cancer Institute cancer center support grant [P30 CA060553]
- Feinberg School of Medicine
- Center for Genetic Medicine
- Feinberg's Department of Biochemistry and Molecular Genetics
- Office of the Provost
- Office for Research
- Northwestern Information Technology
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 monocyte-derived alveolar macrophages persisted in the lung for one year after the resolution of fibrosis, where they became increasingly similar to tissue-resident alveolar macrophages. Human homologues of profibrotic genes expressed by mouse monocyte-derived alveolar macrophages during fibrosis were up-regulated in human alveolar macrophages from fibrotic compared with normal lungs. Our findings suggest that selectively targeting alveolar macrophage differentiation within the lung may ameliorate fibrosis without the adverse consequences associated with global monocyte or tissue-resident alveolar macrophage depletion.
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