The DOI matches its Crossref record; 129 of the 129 references it cites were found in a registry or an index.
Macrophages in Tissue Repair, Regeneration, and Fibrosis
Open accessAbstract
Inflammatory monocytes and resident tissue macrophages are key regulators of tissue repair, regeneration, and fibrosis. Following tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, with uncontrolled inflammatory mediator and growth factor production, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contributing to a state of persistent injury, which may lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue regenerating phenotypes following injury, and highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.
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“M1 and M2 macrophages also play coordinating roles in the wound healing process by secreting cytokines, such as IL-6, transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and IL-8, to mobilize peripheral or systemic monocytes and lymphocytes to gather around the wound surface (Snyder et al., 2016;Wynn and Vannella, 2016).”
From Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization (2023) · cites this paper as Wynn and Vannella, 2016
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“M1 macrophages secrete numerous proteolytic enzymes to degrade extracellular matrix (ECM), including collagens, elastin, and fibronectin.”
From Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization (2023) · cites this paper as Wynn and Vannella, 2016
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“M2 macrophages secrete ECM cross-linking enzymes, such as glutaminyl transferase and osteopontin, which promote ECM and cell adhesion”
From Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization (2023) · cites this paper as Wynn and Vannella, 2016
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“suggesting that both macrophages play important roles in collagen deposition (Wynn and Vannella, 2016;Hesketh et al., 2017;Liu et al., 2021).”
From Nanosilver alleviates foreign body reaction and facilitates wound repair by regulating macrophage polarization (2023) · cites this paper as Wynn and Vannella, 2016
Experimental — accuracy not yet measuredIn the citing paper
“Beyond biochemical cues, the biomechanical properties of the fibrotic microenvironment-notably increased matrix stiffness, fluid shear stress, and intercellular tension-are now recognized as active instructors of macrophage polarization (6,74,75).”
From The mechanotransduction-immune axis in organ fibrosis: dual regulatory mechanisms and translational therapeutic perspectives (2025) · cites this paper as [74]
In the citing paper
“pro-fibrotic macrophages commonly coordinate scar formation via a range of interactions with fibroblasts, the major cellular source of pathological extracellular matrix deposition during fibrosis18,27,74–78.”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [76]
In the citing paper
“M1 macrophages suppress, and M2 macrophages promote, fibroproliferation and uncontrolled repair (17).”
From The Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis (2018) · cites this paper as [17]
In the citing paper
“M1 macrophages suppress, and M2 macrophages promote, fibroproliferation and uncontrolled repair (17).”
From The Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis (2018) · cites this paper as [17]
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1 retracted
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RetractedExploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144
Macrophage activation and polarization: nomenclature and experimental guidelines
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Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335
Protective and pathogenic functions of macrophage subsets
Murray, P. J., & Wynn, T. A. (2011) · Nature Reviews Immunology · doi:10.1038/nri3073 · Cited by 5,269
Self-citationMacrophage biology in development, homeostasis and disease
Wynn, T. A., Chawla, A., & Pollard, J. W. (2013) · Nature · doi:10.1038/nature12034 · Cited by 4,684
Self-citationCellular and molecular mechanisms of fibrosis
Wynn, T. (2008) · The Journal of Pathology · doi:10.1002/path.2277 · Cited by 4,495
Self-citationCirculating mitochondrial DAMPs cause inflammatory responses to injury
Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010) · Nature · doi:10.1038/nature08780 · Cited by 3,812
Mechanisms of fibrosis: therapeutic translation for fibrotic disease
Wynn, T. A., & Ramalingam, T. R. (2012) · Nature Medicine · doi:10.1038/nm.2807 · Cited by 3,541
Self-citationThe regulation of IL-10 production by immune cells
Saraiva, M., & O’Garra, A. (2010) · Nature reviews. Immunology · doi:10.1038/nri2711 · Cited by 3,293
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Metadata
- Authors
- Wynn, T. A., & Vannella, K. M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Wynn, Thomas A.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 44
- Issue
- 3
- Pages
- 450-462
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4794754
- OpenAlex
- W2301044272
- Semantic Scholar
- 3e7cc72db53c49f88a543c99b71749931fb6c7b0
- Cited by
- 4,481
- References
- 129
- Citations by year
- 2026: 673 · 2025: 638 · 2024: 564 · 2023: 511 · 2022: 504 · 2021: 475 · 2020: 399 · 2019: 299 · 2018: 228 · 2017: 136 · 2016: 35
- FWCI
- 29.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (Z01AI001019, Z01AI000829)
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- macrophages, tissue repair, tissue regeneration, fibrosis, inflammatory monocytes, macrophage polarization, wound healing, inflammation resolution, macrophage-targeted therapy
- MeSH terms
- Animals, Cell Communication, Cell Differentiation, Fibrosis, Humans, Macrophage Activation, Macrophages, Phenotype, Regeneration, Wound Healing
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