Sleep modulates haematopoiesis and protects against atherosclerosis

Cameron S. McAlpine, Máté G. Kiss, Sara Rattik, Shun He, Anne Vassalli, Colin Valet, Atsushi Anzai, Christopher T. Chan, John E. Mindur, Florian Kahles, Wolfram C. Poller, Vanessa Frodermann, Ashley M. Fenn, Annemijn F. Gregory, Lennard Halle, Yoshiko Iwamoto, Friedrich F. Hoyer, Christoph J. Binder, Peter Libby, Mehdi TaftiThomas E. Scammell, Matthias Nahrendorf, Filip K. Swirski

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Sleep is integral to life1. Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease2, we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice. We show that mice subjected to sleep fragmentation produce more Ly-6Chigh monocytes, develop larger atherosclerotic lesions and produce less hypocretin—a stimulatory and wake-promoting neuropeptide—in the lateral hypothalamus. Hypocretin controls myelopoiesis by restricting the production of CSF1 by hypocretin-receptor-expressing pre-neutrophils in the bone marrow. Whereas hypocretin-null and haematopoietic hypocretin-receptor-null mice develop monocytosis and accelerated atherosclerosis, sleep-fragmented mice with either haematopoietic CSF1 deficiency or hypocretin supplementation have reduced numbers of circulating monocytes and smaller atherosclerotic lesions. Together, these results identify a neuro-immune axis that links sleep to haematopoiesis and atherosclerosis.

Original languageEnglish
Pages (from-to)383-387
Number of pages5
JournalNature
Volume566
Issue number7744
DOIs
Publication statusPublished - 2019 Feb 21
Externally publishedYes

ASJC Scopus subject areas

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    McAlpine, C. S., Kiss, M. G., Rattik, S., He, S., Vassalli, A., Valet, C., Anzai, A., Chan, C. T., Mindur, J. E., Kahles, F., Poller, W. C., Frodermann, V., Fenn, A. M., Gregory, A. F., Halle, L., Iwamoto, Y., Hoyer, F. F., Binder, C. J., Libby, P., ... Swirski, F. K. (2019). Sleep modulates haematopoiesis and protects against atherosclerosis. Nature, 566(7744), 383-387. https://doi.org/10.1038/s41586-019-0948-2