Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth
Open accessAbstract
Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1(+) precursors and postnatally from bone marrow-derived monocytes that colonize the tissue immediately after birth. In adulthood, proliferation (rather than monocyte recruitment) sustains arterial macrophages in the steady state and after severe depletion following sepsis. After infection, arterial macrophages return rapidly to functional homeostasis. Finally, survival of resident arterial macrophages depends on a CX3CR1-CX3CL1 axis within the vascular niche.
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In adult mice at steady state, nonclassical Ly6Clow monocytes patrol microcirculation vessels and are important for endothelial homeostasis and inflammation.
“In adult mice under physiological, steady-state conditions, the circulating, nonclassical Ly6Clow monocytes remain in the circulation and patrol the vessels of the microcirculation, where these monocytes are critical for endothelial homeostasis and inflammation145.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [145]
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References 48 · Cited by 372
- Authors
- Ensan, S., Li, A., Besla, R., Degousee, N., Cosme, J., Roufaiel, M., Shikatani, E. A., El-Maklizi, M., Williams, J. W., Robins, L., Li, C., Lewis, B., Yun, T. J., Lee, J. S., Wieghofer, P., Khattar, R., Farrokhi, K., Byrne, J., Ouzounian, M., Zavitz, C. C. J., Levy, G. A., Bauer, C. M. T., Libby, P., Husain, M., Swirski, F. K., Cheong, C., Prinz, M., Hilgendorf, I., Randolph, G. J., Epelman, S., Gramolini, A. O., Cybulsky, M. I., Rubin, B. B., & Robbins, C. S.
- Affiliations
- University of Toronto (CA)
- University Health Network (CA)
- Washington University in St. Louis (US)
- Montreal Clinical Research Institute (CA)
- University of Freiburg (DE)
- F. Hoffmann-La Roche AG (CH)
- Brigham and Women's Hospital (US)
- Corresponding author
- Robbins, Clinton S
- ORCID
- Besla, Rickvinder
- Cosme, Jake
- Roufaiel, Mark
- El-Maklizi, Mahmoud
- Williams, Jesse W
- Yun, Tae Jin
- Lee, Jun Seong
- Wieghofer, Peter
- Khattar, Ramzi
- Farrokhi, Kaveh
- Byrne, John
- Ouzounian, Maral
- Levy, Gary A
- Libby, Peter
- Husain, Mansoor
- Cheong, Cheolho
- Prinz, Marco
- Hilgendorf, Ingo
- Randolph, Gwendalyn J
- Epelman, Slava
- Gramolini, Anthony O
- Cybulsky, Myron I
- Rubin, Barry B
- Robbins, Clinton S
- Venue
- Nature Immunology
- Published
- 2015-12-07
- Volume
- 17
- Issue
- 2
- Pages
- 159-168
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2242760558
- Cited by
- 372
- References
- 48
- Citations by year
- 2026: 26 · 2025: 28 · 2024: 39 · 2023: 25 · 2022: 45 · 2021: 34 · 2020: 37 · 2019: 33 · 2018: 35 · 2017: 40 · 2016: 28 · 2015: 1
- FWCI
- 17.09
- Type
- journal article
- Language
- en
- Open access
- green
- nrs.harvard.edu
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- OPUS (Augsburg University) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (MOP133390)
- National Institute of Allergy and Infectious Diseases (R01AI049653)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- macrophage origin, bone marrow-derived monocytes, monocyte recruitment, macrophage homeostasis, macrophage proliferation, sepsis, infection, vascular niche
- MeSH terms
- Cell Self Renewal, CX3C Chemokine Receptor 1, Animals, Cell Survival, Female, Macrophages, Male, Mice, Transgenic, Monocytes, Phenotype, Protein Binding, Cluster Analysis, Immunophenotyping, Receptors, Chemokine, Gene Expression Profiling, Mice, Embryonic Stem Cells, Chemokine CX3CL1, Stem Cell Niche, Transcriptome
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