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

By Amit A. Patel, Yan Zhang, J. Fullerton, Lies Boelen, A. Rongvaux, Alexander A. Maini, V. Bigley, R. Flavell, D. Gilroy, Becca Asquith and 2 more. Journal of Experimental Medicine, 2017

854 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/21efb2852a3a35fc5f1f3312e973784b7a6656f0

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In Immunology

1. A. Mildner
2. L. Cañedo-Dorantes
3. Mara Cañedo-Ayala
4. Joachim L. Schultze
5. S. Yona
6. M. Guilliams

Citations in the corpus

• Skin Acute Wound Healing: A Comprehensive Review (2019, background): “In a recent study of in vivo leukocyte kinetics using deuterium labeling, a sequential transition from monocyte progenitors to nonclassical monocytes was reported [58].”
• Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases (2019, background): “Investigation in the developmental trajectories of the three described monocyte subsets with deuterium labeling in humans suggested that intermediate and non-classical monocytes emerge sequentially from the pool of classical monocytes (10).”
• Developmental and Functional Heterogeneity of Monocytes. (2018, background): “Mathematical modelling of the conversion rate of classical to non-classical monocytes based on pulse labelling decay in comparison to the extravasation rate into tissues indicates that vast majority of classical monocytes are recruited to peripheral tissues where they potentially differentiate into ”