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The fate and lifespan of human monocyte subsets in steady state and systemic inflammation
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In humans, the monocyte pool comprises three subsets (classical, intermediate, and nonclassical) that circulate in dynamic equilibrium. The kinetics underlying their generation, differentiation, and disappearance are critical to understanding both steady-state homeostasis and inflammatory responses. Here, using human in vivo deuterium labeling, we demonstrate that classical monocytes emerge first from marrow, after a postmitotic interval of 1.6 d, and circulate for a day. Subsequent labeling of intermediate and nonclassical monocytes is consistent with a model of sequential transition. Intermediate and nonclassical monocytes have longer circulating lifespans (∼4 and ∼7 d, respectively). In a human experimental endotoxemia model, a transient but profound monocytopenia was observed; restoration of circulating monocytes was achieved by the early release of classical monocytes from bone marrow. The sequence of repopulation recapitulated the order of maturation in healthy homeostasis. This developmental relationship between monocyte subsets was verified by fate mapping grafted human classical monocytes into humanized mice, which were able to differentiate sequentially into intermediate and nonclassical cells.
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“Similarly, in humans, the nonclassical CD14+CD16+ monocytes normally remain in the blood circulation, where they patrol the endothelium to scan the integrity of endothelial cells147.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [147]
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Metadata
- Authors
- Patel, A. A., Zhang, Y., Fullerton, J. N., Boelen, L., Rongvaux, A., Maini, A. A., Bigley, V., Flavell, R. A., Gilroy, D. W., Asquith, B., Macallan, D., & Yona, S.
- Affiliations
- University of London (GB)
- St George's, University of London (GB)
- Imperial College London (GB)
- Yale University (US)
- Newcastle University (GB)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Yona, Simon
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2017-06-12
- Volume
- 214
- Issue
- 7
- Pages
- 1913-1923
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC5502436
- OpenAlex
- W2626120438
- Cited by
- 946
- References
- 64
- Citations by year
- 2026: 67 · 2025: 111 · 2024: 126 · 2023: 104 · 2022: 120 · 2021: 114 · 2020: 126 · 2019: 94 · 2018: 76 · 2017: 8
- FWCI
- 37.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Engineering and Physical Sciences Research Council
- Wellcome Trust (093053/Z/10/Z, 103865)
- Medical Research Council (G1001052, J007439)
- Bloodwise (15012)
- European Union Seventh Framework Program (FP7/2007–2013, 317040)
- Leukemia and Lymphoma Research (15012)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- monocyte subsets, classical monocytes, intermediate monocytes, non-classical monocytes, systemic inflammation, endotoxemia, monocytopenia, monocyte differentiation, fate mapping, humanized mice, deuterium labeling
- MeSH terms
- Animals, Bone Marrow Cells, Cell Differentiation, Cell Survival, Cells, Cultured, Deuterium, Flow Cytometry, Homeostasis, Humans, Inflammation, Isotope Labeling, Monocytes, Time Factors, Endotoxemia, Mice
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