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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In humans, nonclassical CD14+CD16+ monocytes normally stay in blood and patrol endothelium to monitor endothelial integrity.
“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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Self-citationA lipid atlas of human and mouse immune cells provides insights into ferroptosis susceptibility
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- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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