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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

580 Scopus citations

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.

Original languageAmerican English
Pages (from-to)1913-1923
Number of pages11
JournalJournal of Experimental Medicine
Volume214
Issue number7
DOIs
StatePublished - 1 Jul 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Patel et al.

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