Sleep modulates haematopoiesis and protects against atherosclerosis

• Published in: Nature (London) 2019-02, Vol.566 (7744), p.383-387
• Main Authors: McAlpine, Cameron S., Kiss, Máté G., Rattik, Sara, He, Shun, Vassalli, Anne, Valet, Colin, Anzai, Atsushi, Chan, Christopher T., Mindur, John E., Kahles, Florian, Poller, Wolfram C., Frodermann, Vanessa, Fenn, Ashley M., Gregory, Annemijn F., Halle, Lennard, Iwamoto, Yoshiko, Hoyer, Friedrich F., Binder, Christoph J., Libby, Peter, Tafti, Mehdi, Scammell, Thomas E., Nahrendorf, Matthias, Swirski, Filip K.
• Format: Article
• Language: English
• Subjects: 13/1; 13/21; 13/31; 14/34; 14/63; 38/35; 38/77; 45/77; 631/250/256; 631/443/592; 64/60; 692/308/1426; 82/1; 96/100; Alzheimer's disease; Animals; Antigens, Ly - metabolism; Arteriosclerosis; Atherosclerosis; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - prevention & control; Bone marrow; Bone Marrow Cells - metabolism; Cardiovascular diseases; Development and progression; Female; Health; Health aspects; Hematopoiesis; Hematopoiesis - drug effects; Hematopoiesis - physiology; Humanities and Social Sciences; Hypothalamic Area, Lateral - metabolism; Hypothalamus; Hypothalamus (lateral); Lesions; Letter; Leukocytes (neutrophilic); Ly-6 antigen; Macrophage Colony-Stimulating Factor - biosynthesis; Macrophage Colony-Stimulating Factor - deficiency; Macrophage Colony-Stimulating Factor - metabolism; Male; Mice; Molecular modelling; Monocytes - drug effects; Monocytes - metabolism; Monocytosis; multidisciplinary; Myelopoiesis; Myelopoiesis - drug effects; Nervous system; Neuropeptides; Neutrophils; Neutrophils - metabolism; Orexin Receptors - deficiency; Orexin Receptors - metabolism; Orexins; Orexins - biosynthesis; Orexins - deficiency; Orexins - metabolism; Orexins - pharmacology; Physiological aspects; Risk factors; Rodents; Science; Science (multidisciplinary); Sleep; Sleep - drug effects; Sleep - physiology; Sleep Deprivation - metabolism; Sleep Deprivation - physiopathology; Sleep Deprivation - prevention & control; Sleep disorders; Stem cells; Supplements
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-019-0948-2

Sleep is integral to life 1 . Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease 2 , 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-6C high 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. The fragmentation of sleep in Apoe −/− mice induces monocytosis and accelerated atherosclerosis due to a reduction in hypocretin that otherwise restricts bone marrow CSF1 availability.