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

Patel, AA; Zhang, Y; Fullerton, JN; Boelen, L; Rongvaux, A; Maini, AA; Bigley, V; ... Yona, S; + view all (2017) The fate and lifespan of human monocyte subsets in steady state and systemic inflammation. Journal of Experimental Medicine , 214 (7) pp. 1913-1923. 10.1084/jem.20170355. Green open access

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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.

Type: Article
Title: The fate and lifespan of human monocyte subsets in steady state and systemic inflammation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1084/jem.20170355
Publisher version: http://doi.org/10.1084/jem.20170355
Language: English
Additional information: © 2017 Patel et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
Keywords: inflammation, monocytes, steady state, deuterium, kinetics, mice, bone marrow
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1559696
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