Cited by 949Immune cells in cancerImmune Response and InflammationImmune responses and vaccinations

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The fate and lifespan of human monocyte subsets in steady state and systemic inflammation

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Patel, Amit A., Zhang, Yan, Fullerton, James N., Boelen, Lies, Rongvaux, Anthony, Maini, Alexander A., Bigley, Venetia, Flavell, Richard A., Gilroy, Derek W., Asquith, Becca, Macallan, Derek, Yona, Simon·2017·Journal of Experimental Medicine

DOI 10.1084/jem.20170355PMC PMC5502436

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Abstract

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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Additional file 2 of An epigenetic and transcriptomic signature of immune tolerance in human monocytes through multi-omics integration
Brands, X., Haak, B. W., Klarenbeek, A. M., Butler, J. M., Uhel, F., Qin, W., Otto, N. A., Jakobs, M. E., Faber, D. R., Lutter, R., et al. (2021) · Figshare · doi:10.6084/m9.figshare.15179234
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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: Patel, Amit A.
Zhang, Yan
Fullerton, James N.
Boelen, Lies
Rongvaux, Anthony
Maini, Alexander A.
Bigley, Venetia
Flavell, Richard A.
Gilroy, Derek W.
Asquith, Becca
Macallan, Derek
Yona, Simon
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
DOI: 10.1084/jem.20170355
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
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor, 830 d)
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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The fate and lifespan of human monocyte subsets in steady state and systemic inflammation

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