The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Differential Roles of Macrophages in Diverse Phases of Skin Repair
Abstract
Influx of macrophages plays a crucial role in tissue repair. However, the precise function of macrophages during the healing response has remained a subject of debate due to their functional dichotomy as effectors of both tissue injury and repair. We tested the hypothesis that macrophages recruited during the diverse phases of skin repair after mechanical injury exert specific functions to restore tissue integrity. For this purpose, we developed a mouse model that allows conditional depletion of macrophages during the sequential stages of the repair response. Depletion of macrophages restricted to the early stage of the repair response (inflammatory phase) significantly reduced the formation of vascularized granulation tissue, impaired epithelialization, and resulted in minimized scar formation. In contrast, depletion of macrophages restricted to the consecutive mid-stage of the repair response (phase of tissue formation) resulted in severe hemorrhage in the wound tissue. Under these conditions, transition into the subsequent phase of tissue maturation and wound closure did not occur. Finally, macrophage depletion restricted to the late stage of repair (phase of tissue maturation) did not significantly impact the outcome of the repair response. These results demonstrate that macrophages exert distinct functions during the diverse phases of skin repair, which are crucial to control the natural sequence of repair events.
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In the citing paper
“In both conditions, progression to the following phases of wound repair fails [83].”
From Transition from inflammation to proliferation: a critical step during wound healing (2016) · cites this paper as [83]
In the citing paper
“Their study shows that when macrophages are absent in the inflammatory phase, re-epithelialization and granulation tissue formation are reduced; whereas depletion of macrophages in the proliferative phase results in haemorrhage [83].”
From Transition from inflammation to proliferation: a critical step during wound healing (2016) · cites this paper as [83]
In the citing paper
“Their study shows that when macrophages are absent in the inflammatory phase, re-epithelialization and granulation tissue formation are reduced; whereas depletion of macrophages in the proliferative phase results in haemorrhage [83].”
From Transition from inflammation to proliferation: a critical step during wound healing (2016) · cites this paper as [83]
In the citing paper
“A recent study showed that depletion of macrophages during the proliferative phase of wound healing resulted in a defective transition to the remodeling phase and impaired healing [106,107].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [106]
Citations
Cites
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144
Gurtner, G. C., Werner, S., Barrandon, Y., & Longaker, M. T. (2008) · Nature · doi:10.1038/nature07039 · Cited by 6,542
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190
Myofibroblasts and mechano-regulation of connective tissue remodelling
Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C., & Brown, R. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm809 · Cited by 4,290
VEGF receptor signalling ? in control of vascular function
Olsson, A.-K., Dimberg, A., Kreuger, J., & Claesson-Welsh, L. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1911 · Cited by 3,122
Inflammation in Wound Repair: Molecular and Cellular Mechanisms
Eming, S. A., Krieg, T., & Davidson, J. M. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700701 · Cited by 2,429
Self-citationNahrendorf, M., Swirski, F. K., Aikawa, E., Stangenberg, L., Wurdinger, T., Figueiredo, J.-L., Libby, P., Weissleder, R., & Pittet, M. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070885 · Cited by 2,300
Arnold, L., Henry, A., Poron, F., Baba-Amer, Y., van Rooijen, N., Plonquet, A., Gherardi, R. K., & Chazaud, B. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070075 · Cited by 2,002
Inflammatory cells during wound repair: the good, the bad and the ugly
Martin, P., & Leibovich, S. J. (2005) · Trends in Cell Biology · doi:10.1016/j.tcb.2005.09.002 · Cited by 1,340 · cited 1×
“Their number increases during the phase of inflammation, peaks during the phase of tissue formation, and gradually declines during the maturation phase (9).”
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Flagged first, then by citations
Research works printed but not linked: 32
- Babcock, 2008, Circulating blood cells function as a surveillance system for damaged tissue in Drosophila larvae., Proc. Natl. Acad. Sci. USA, 105, 10017, 10.1073/pnas.0709951105 · DOI
- Niethammer, 2009, A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish., Nature, 459, 996, 10.1038/nature08119 · DOI · Paper page
- Chen, 2009, C/EBPalpha initiates primitive myelopoiesis in pluripotent embryonic cells., Blood, 114, 40, 10.1182/blood-2008-11-189159 · DOI
- Werner, 2007, Keratinocyte-fibroblast interactions in wound healing., J. Invest. Dermatol., 127, 998, 10.1038/sj.jid.5700786 · DOI
- Eming, 2009, Interrelation of immunity and tissue repair or regeneration., Semin. Cell Dev. Biol., 20, 517, 10.1016/j.semcdb.2009.04.009 · DOI · Paper page
- Loots, 1998, Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds., J. Invest. Dermatol., 111, 850, 10.1046/j.1523-1747.1998.00381.x · DOI · Paper page
- Simpson, 1972, The neutrophilic leukocyte in wound repair a study with antineutrophil serum., J. Clin. Invest., 51, 2009, 10.1172/JCI107007 · DOI · Paper page
- Leibovich, 1975, The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum., Am. J. Pathol., 78, 71
- Martin, 2003, Wound healing in the PU.1 null mouse—tissue repair is not dependent on inflammatory cells., Curr. Biol., 13, 1122, 10.1016/S0960-9822(03)00396-8 · DOI
- Werner, 2003, Regulation of wound healing by growth factors and cytokines., Physiol. Rev., 83, 835, 10.1152/physrev.2003.83.3.835 · DOI · Paper page
- Eming, 2007, Accelerated wound closure in mice deficient for interleukin-10., Am. J. Pathol., 170, 188, 10.2353/ajpath.2007.060370 · DOI
- Ishida, 2008, Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and fibroblast accumulation and function., J. Immunol., 180, 569, 10.4049/jimmunol.180.1.569 · DOI · Paper page
- Han, 2008, Development and regeneration of the neonatal digit tip in mice., Dev. Biol., 315, 125, 10.1016/j.ydbio.2007.12.025 · DOI
- Buch, 2005, A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration., Nat. Methods, 2, 419, 10.1038/nmeth762 · DOI
- Clausen, 1999, Conditional gene targeting in macrophages and granulocytes using LysMcre mice., Transgenic Res., 8, 265, 10.1023/A:1008942828960 · DOI · Paper page
- Cazac, 2000, TGF-beta receptor controls B cell responsiveness and induction of IgA in vivo., Immunity, 13, 443, 10.1016/S1074-7613(00)00044-3 · DOI
- Raes, 2002, Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages., J. Leukoc. Biol., 71, 597, 10.1189/jlb.71.4.597 · DOI
- Nair, 2003, Macrophages in chronic type 2 inflammation have a novel phenotype characterized by the abundant expression of Ym1 and Fizz1 that can be partly replicated in vitro., Immunol. Lett., 85, 173, 10.1016/S0165-2478(02)00225-0 · DOI
- Benjamin, 1998, A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF., Development, 125, 1591, 10.1242/dev.125.9.1591 · DOI
- Roth, 2006, Plasmin modulates vascular endothelial growth factor-A-mediated angiogenesis during wound repair., Am. J. Pathol., 168, 670, 10.2353/ajpath.2006.050372 · DOI · Paper page
- Alon, 1995, Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity., Nat. Med., 1, 1024, 10.1038/nm1095-1024 · DOI
- Carvalho, 2007, Compensatory signalling induced in the yolk sac vasculature by deletion of TGFbeta receptors in mice., J. Cell Sci., 120, 4269, 10.1242/jcs.013169 · DOI
- McCartney-Francis, 1990, TGF-beta regulates production of growth factors and TGF-beta by human peripheral blood monocytes., Growth Factors, 4, 27, 10.3109/08977199009011007 · DOI
- Duffield, 2003, The inflammatory macrophage: a story of Jekyll and Hyde., Clin. Sci. (Lond.), 104, 27, 10.1042/cs1040027 · DOI
- Duffield, 2005, Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair., J. Clin. Invest., 115, 56, 10.1172/JCI200522675 · DOI · Paper page
- Kim, 2008, Dynamics of neutrophil infiltration during cutaneous wound healing and infection using fluorescence imaging., J. Invest. Dermatol., 128, 1812, 10.1038/sj.jid.5701223 · DOI
- Mirza, 2009, Selective and specific macrophage ablation is detrimental to wound healing in mice., Am. J. Pathol., 175, 2454, 10.2353/ajpath.2009.090248 · DOI · Paper page
- Martinez, 2009, Alternative activation of macrophages: an immunologic functional perspective., Annu. Rev. Immunol., 27, 451, 10.1146/annurev.immunol.021908.132532 · DOI · Paper page
- Pull, 2005, Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury., Proc. Natl. Acad. Sci. USA, 102, 99, 10.1073/pnas.0405979102 · DOI
- ten Dijke, 2007, Extracellular control of TGFbeta signalling in vascular development and disease., Nat. Rev. Mol. Cell Biol., 8, 857, 10.1038/nrm2262 · DOI
- Li, 2006, Transforming growth factor-beta regulation of immune responses., Annu. Rev. Immunol., 24, 99, 10.1146/annurev.immunol.24.021605.090737 · DOI
- Kümin, 2007, Peroxiredoxin 6 is required for blood vessel integrity in wounded skin., J. Cell Biol., 179, 747, 10.1083/jcb.200706090 · DOI
Cited by
Sorted by citations
Items 1,001–1,005 of 1,005
Feng, X., Wu, Q., Yan, Y., Yu, B., Zhu, Z., Qiao, Y., & Wei, J. (2026) · Stem Cell Reviews and Reports · doi:10.1007/s12015-026-11202-9
Immune-Phase-Aware Protein Delivery via Polymeric Nanomedicines for Tissue Regeneration: A Review
Yang, S.-H., Lu, S.-C., Cai, F.-C., & Hsu, R. (2026) · ACS Applied Nano Materials · doi:10.1021/acsanm.6c01967
Hosomi, K., Nagata, M., Okada, M., Hirano, K., Yamada, E., Nakagawa, T., Maruyama, K., Banda, C., Shiraishi, M., Danno, K., et al. (2026) · Inflammation and Regeneration · doi:10.1186/s41232-026-00438-0
Loss of tissue-state plasticity: a conceptual framework for age-associated regenerative failure
Otsuka, T., & Matsui, H. (2026) · Inflammation and Regeneration · doi:10.1186/s41232-026-00435-3
“…studies on skin repair have demonstrated that fibrotic or regenerative outcomes are strongly influenced by the composition of distinct fibroblast lineages, wound microenvironment, and inflammatory conditions, rather than being uniformly determined by growth factor signaling alone [41, 53–55].”
Yoon, A., Han, J.-H., Oh, J., Shin, K., & Hur, J. (2026) · Life Sciences · doi:10.1016/j.lfs.2026.124577
Metadata
- Authors
- Lucas, T., Waisman, A., Ranjan, R., Roes, J., Krieg, T., Müller, W., Roers, A., & Eming, S. A.
- Affiliations
- Department of Dermatology
- Johannes Gutenberg University Mainz (DE)
- University College London (GB)
- University of Cologne (DE)
- University of Manchester (GB)
- Technische Universität Dresden (DE)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-04-01
- Volume
- 184
- Issue
- 7
- Pages
- 3964-3977
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2118654016
- Cited by
- 1,205
- References
- 0
- Citations by year
- 2026: 47 · 2025: 71 · 2024: 84 · 2023: 86 · 2022: 110 · 2021: 102 · 2020: 90 · 2019: 76 · 2018: 87 · 2017: 83 · 2016: 73 · 2015: 78 · 2014: 73 · 2013: 66 · 2012: 41
- FWCI
- 47.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- University College London
- Deutsche Forschungsgemeinschaft (SFB829)
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- macrophages, skin repair, wound healing, mechanical damage, granulation tissue, re-epithelialization, scar formation, hemorrhage, tissue maturation, wound closure, tissue formation
- MeSH terms
- Animals, Cell Separation, Flow Cytometry, Immunohistochemistry, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Skin, Skin Physiological Phenomena, Wound Healing, Reverse Transcriptase Polymerase Chain Reaction, Mice
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