ArticleThe Journal of experimental medicine2017
Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span.
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Article in The Journal of experimental medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 773 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
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773citing papers in PubMed, 2 pooled it
67.1field-weighted citation impact, top 1% of its field
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Who cites it
773 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,107 citations in OpenAlex.
- The Role of Monocytes in the Natural History of Idiopathic Pulmonary Fibrosis: A Systematic Literature Review.International journal of molecular sciences · 2025Pooled it
- Targeted therapy for idiopathic pulmonary fibrosis: a bibliometric analysis of 2004-2024.Frontiers in medicine · 2025Pooled it
- Antifibrotic monocyte activation by nanoparticles resolves murine pulmonary fibrosis.Biomaterials · 2026Article
- Monocytes in pneumonia: Functional plasticity and innate memory (Review).International journal of molecular medicine · 2026Review
- Alveolar Macrophages: Development, Respiratory Homeostasis, Signal Pathways, Diseases, and Therapeutic Opportunities.MedComm · 2026Review
- Monocyte-derived galectin-1Nature immunology · 2026Article
- Transcriptional factor KLF9 in pulmonary fibrosis: from molecular mechanisms to precision intervention-a narrative review.Journal of thoracic disease · 2026Review
- Article
- Tissue-Resident Macrophages: Linking Physiology and Inflammation in Infection.Clinical reviews in allergy & immunology · 2026Review
- Macrophage heterogeneity in human secondary lymphoid organs.Clinical science (London, England : 1979) · 2026Review
- Milk-derived extracellular vesicles loaded with miR-146a-5p as a novel therapeutic strategy for allergic airway inflammation.Molecular therapy. Nucleic acids · 2026Article
- Macrophage heterogeneity in organ fibrosis in the era of single-cell omics.Molecular biology reports · 2026Review
- Angiogenesis in Lung Regeneration and Aging.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Non-Resolving Repair in Idiopathic Pulmonary Fibrosis: From Failed Cellular Transitions to Architectural Lock-In.International journal of molecular sciences · 2026Review
- Amniotic Mesenchymal Stromal Cell Administration Prevents and Stops Lung Fibrosis and Is Associated with Distinct Macrophage Signatures.Pharmaceutics · 2026Article
- Cytoskeletal-nuclear control of alveolar fibroblast identity directs lung regeneration.bioRxiv : the preprint server for biology · 2026Article
- The Therapeutic Efficacy of Inhaled Vitamin D3 Metabolites Initiated During the Acute Phase of Hypersensitivity Pneumonitis: An In Vivo Study.Molecules (Basel, Switzerland) · 2026Article
- Blocking interleukin 33 reduces joint, systemic, and lung inflammatory responses in the combined collagen-induced arthritis-inhalant endotoxin exposure model.The Journal of pharmacology and experimental therapeutics · 2026Article
- Alveolar macrophage-derived TGF-β promotes acute lung injury recovery by regulating inflammatory monocyte-derived macrophages.Journal of advanced research · 2026Article
- Capturing the dynamics of STAT6 macrophage polarization using bioluminescence temporal signatures.Cell systems · 2026Article
713 more citing papers are in PubMed but not listed here.
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Authors and funding
43 authors at 3 institutions in 1 country.
Alexander V MisharinDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0003-2879-3789
Luisa Morales-NebredaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Paul A ReyfmanDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0002-6435-6001
Carla M CudaDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
James M WalterDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Alexandra C McQuattie-PimentelDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0003-4028-9905
Ching-I ChenDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Kishore R AnekallaDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Nikita JoshiDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Kinola J N WilliamsDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Hiam Abdala-ValenciaDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Tyrone J YacoubDepartment of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL.
Monica ChiDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Stephen ChiuDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0003-2759-9394
Francisco J Gonzalez-GonzalezDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0003-3662-8695
Khalilah GatesDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Anna P LamDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0001-9998-297X
Trevor T NicholsonDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0003-3187-1493
Philip J HomanDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Saul SoberanesDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Salina DominguezDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Vince K MorganDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0001-6162-0463
Rana SaberDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Alexander ShafferDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0002-9620-4803
Monique HinchcliffDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Stacy A MarshallDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Ankit BharatDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Sergejs BerdnikovsDivision of Allergy and Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Sangeeta M BhoradeDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Elizabeth T BartomDivision of Thoracic Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0002-5618-2582
Richard I MorimotoDepartment of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL.ORCID http://orcid.org/0000-0002-3431-445X
William E BalchDepartment of Molecular Medicine, The Scripps Research Institutes, La Jolla, CA.
Jacob I SznajderDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0002-2089-4764
Navdeep S ChandelDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Gökhan M MutluSection of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL.ORCID http://orcid.org/0000-0002-2056-612X
Manu JainDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Cara J GottardiDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0003-0912-7617
Benjamin D SingerDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.ORCID http://orcid.org/0000-0001-5775-8427
Karen M RidgeDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Neda BagheriDivision of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL.
Ali ShilatifardDivision of Thoracic Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL.
G R Scott BudingerDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL s-buding@northwestern.edu.
Harris PerlmanDepartment of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL h-perlman@northwestern.edu.ORCID http://orcid.org/0000-0003-4174-608X
Northwestern University · USScripps Research Institute · USUniversity of Chicago · US
Funding
Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1993 to 2026
$153.9MNorthwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8MRole of LUBAC and Na K-ATPase in Acute Lung InjuryP01HL071643 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SZNAJDER, JACOB I · 2003 to 2019
$30.8MTissue resident macrophages regulate proteostasis in the aging lungP01AG049665 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KAREN M RIDGE · 2015 to 2026
$26.9MTraining Program In Lung SciencesT32HL076139 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KAREN M RIDGE, Jacob I Sznajder · 2004 to 2026
$9.6MSystems Genetics Approach to Gene Discovery in Chronic RhinosinusitisU19AI106683 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KERN, ROBERT C · 2014 to 2017
$7.9MRole of alveolar macrophages in particulate matter-induced cardiopulmonary diseaseR01ES015024 · NIEHS · UNIVERSITY OF CHICAGO · PI MUTLU, GOKHAN M. · 2006 to 2022
$6.1MThe injurious effects of hypercapnia on the alveolar epitheliumR01HL085534 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SZNAJDER, JACOB I · 2006 to 2018
$4.9MRole and Regulation of Sodium, Potasium ATPase in LungR37HL048129 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SZNAJDER, JACOB I · 2008 to 2017
$4.0MC. elegans Model for Neurodegenerative Diseases of AgingR37AG026647 · NIA · NORTHWESTERN UNIVERSITY · PI MORIMOTO, RICHARD I · 2010 to 2019
$3.9MTransplant Surgery Scientist Training ProgramT32DK077662 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Richard M Green, Daniela P Ladner · 2007 to 2026
$3.8MSignaling in the lung induced by particulate matter air pollutionR01ES013995 · NIEHS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BUDINGER, GR SCOTT · 2006 to 2015
$3.3MBLRD VA I01 BX000201NCATS NIH HHS UL1 TR001422NCI NIH HHS P30 CA060553NHLBI NIH HHS F32 HL136111NHLBI NIH HHS K08 HL125940NHLBI NIH HHS K08 HL128867NHLBI NIH HHS P01 HL071643NHLBI NIH HHS R01 HL048129NHLBI NIH HHS R01 HL079190NHLBI NIH HHS R01 HL085534NHLBI NIH HHS R01 HL124664NHLBI NIH HHS R01 HL128194NHLBI NIH HHS R01 HL134375NHLBI NIH HHS R37 HL048129NHLBI NIH HHS R56 HL127245NHLBI NIH HHS T32 HL076139NIAID NIH HHS U19 AI106683NIAMS NIH HHS K01 AR064313NIAMS NIH HHS R01 AR064546NIAMS NIH HHS R03 AR061593NIA NIH HHS P01 AG049665NIA NIH HHS R37 AG026647NIDDK NIH HHS T32 DK077662NIEHS NIH HHS R01 ES013995NIEHS NIH HHS R01 ES015024NIEHS NIH HHS R21 ES025644
Abstract
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.
Indexed as
AnimalsCell DifferentiationFibrosisHumansLungMacrophages, AlveolarMiceMonocytes
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