Date Published:

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 ( approximately 4 and approximately 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.

Notes:

Patel, Amit AZhang, YanFullerton, James NBoelen, LiesRongvaux, AnthonyMaini, Alexander ABigley, VenetiaFlavell, Richard AGilroy, Derek WAsquith, BeccaMacallan, DerekYona, SimonengWellcome Trust/United KingdomG1001052/Medical Research Council/United KingdomMR/J007439/1/Medical Research Council/United KingdomUL1 TR001863/TR/NCATS NIH HHS/J Exp Med. 2017 Jul 3;214(7):1913-1923. doi: 10.1084/jem.20170355. Epub 2017 Jun 12.