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J Exp Med. 2017 Jul 3;214(7):1913-1923. doi: 10.1084/jem.20170355. Epub 2017 Jun 12.

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

Author information

1
Division of Medicine, University College London, University of London, London, England, UK.
2
Institute for Infection and Immunity, St. George's, University of London, London, England, UK.
3
Theoretical Immunology Group, Faculty of Medicine, Imperial College London, London, England, UK.
4
Department of Immunobiology, Yale University, New Haven, CT.
5
Newcastle University Medical School, Newcastle University, Newcastle Upon Tyne, England, UK.
6
Howard Hughes Medical Institute, Yale University, New Haven, CT.
7
St. George's University Hospitals NHS Foundation Trust, London, England, UK.
8
Division of Medicine, University College London, University of London, London, England, UK s.yona@ucl.ac.uk.

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.

PMID:
28606987
PMCID:
PMC5502436
DOI:
10.1084/jem.20170355
[Indexed for MEDLINE]
Free PMC Article

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