TY - JOUR
T1 - Sleep modulates haematopoiesis and protects against atherosclerosis
AU - McAlpine, Cameron S.
AU - Kiss, Máté G.
AU - Rattik, Sara
AU - He, Shun
AU - Vassalli, Anne
AU - Valet, Colin
AU - Anzai, Atsushi
AU - Chan, Christopher T.
AU - Mindur, John E.
AU - Kahles, Florian
AU - Poller, Wolfram C.
AU - Frodermann, Vanessa
AU - Fenn, Ashley M.
AU - Gregory, Annemijn F.
AU - Halle, Lennard
AU - Iwamoto, Yoshiko
AU - Hoyer, Friedrich F.
AU - Binder, Christoph J.
AU - Libby, Peter
AU - Tafti, Mehdi
AU - Scammell, Thomas E.
AU - Nahrendorf, Matthias
AU - Swirski, Filip K.
N1 - Funding Information:
Acknowledgements This work was supported in part by NIH grants R35 HL135752, R01 HL128264, P01 HL131478, an American Heart Association Established Investigator Award, and the Patricia and Scott Eston MGH Research Scholar (to F.K.S.); NIH grant R35 HL139598 (to M.N.); Swiss National Science Foundation grants 31003A_125323 and 31003A_144282 (to A.V.); a CIHR postdoctoral fellowship and a Banting postdoctoral fellowship (to C.S.M.); the doctoral program Cell Communication in Health and Disease (CCHD) funded by the Austrian Science Fund (to M.G.K.); a Swedish Research Council postdoctoral fellowship (to S.R.); an American Heart Association postdoctoral fellowship (to S.H.); a postdoctoral fellowship from the Fondation pour la Recherche Medicale (to C.V.); the German Research Foundation (DFG; 331536185 to F.K. and 398190272 to W.C.P.); and a Boehringer-Ingelheim-Fonds MD fellowship (to L.H.). We thank A. Lichtman for providing the PCSK9 adenovirus, D. Scadden for providing stromal cell reporter mice and K. Joyes for editing the manuscript.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/2/21
Y1 - 2019/2/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85061806855&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061806855&partnerID=8YFLogxK
U2 - 10.1038/s41586-019-0948-2
DO - 10.1038/s41586-019-0948-2
M3 - Article
C2 - 30760925
AN - SCOPUS:85061806855
SN - 1465-7392
VL - 566
SP - 383
EP - 387
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 7744
ER -