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dc.contributor.authorHeidt, Timoen_US
dc.contributor.authorSager, Hendrik B.en_US
dc.contributor.authorCourties, Gabrielen_US
dc.contributor.authorDutta, Parthaen_US
dc.contributor.authorIwamoto, Yoshikoen_US
dc.contributor.authorZaltsman, Alexen_US
dc.contributor.authorvon zur Muhlen, Constantinen_US
dc.contributor.authorBode, Christophen_US
dc.contributor.authorFricchione, Gregory L.en_US
dc.contributor.authorDenninger, Johnen_US
dc.contributor.authorLin, Charles P.en_US
dc.contributor.authorVinegoni, Claudioen_US
dc.contributor.authorLibby, Peteren_US
dc.contributor.authorSwirski, Filip K.en_US
dc.contributor.authorWeissleder, Ralphen_US
dc.contributor.authorNahrendorf, Matthiasen_US
dc.date.accessioned2015-02-02T15:32:50Z
dc.date.issued2014en_US
dc.identifier.citationHeidt, T., H. B. Sager, G. Courties, P. Dutta, Y. Iwamoto, A. Zaltsman, C. von zur Muhlen, et al. 2014. “Chronic variable stress activates hematopoietic stem cells.” Nature medicine 20 (7): 754-758. doi:10.1038/nm.3589. http://dx.doi.org/10.1038/nm.3589.en
dc.identifier.issn1078-8956en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13890692
dc.description.abstractExposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis1,2. While incompletely understood, interaction between the psyche and the immune system provides one potential mechanism linking stress and disease inception and progression. Known crosstalk between the brain and immune system includes the hypothalamic–pituitary–adrenal axis, which centrally drives glucocorticoid production in the adrenal cortex, and the sympathetic–adrenal–medullary axis, which controls stress–induced catecholamine release in support of the fight–or–flight reflex3,4. It remains unknown however if chronic stress changes hematopoietic stem cell activity. Here we show that stress increases proliferation of these most primitive progenitors, giving rise to higher levels of disease–promoting inflammatory leukocytes. We found that chronic stress induced monocytosis and neutrophilia in humans. While investigating the source of leukocytosis in mice, we discovered that stress activates upstream hematopoietic stem cells. Sympathetic nerve fibers release surplus noradrenaline, which uses the β3 adrenergic receptor to signal bone marrow niche cells to decrease CXCL12 levels. Consequently, elevated hematopoietic stem cell proliferation increases output of neutrophils and inflammatory monocytes. When atherosclerosis–prone ApoE−/− mice encounter chronic stress, accelerated hematopoiesis promotes plaque features associated with vulnerable lesions that cause myocardial infarction and stroke in humans.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/nm.3589en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087061/pdf/en
dash.licenseLAAen_US
dc.titleChronic variable stress activates hematopoietic stem cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNature medicineen
dash.depositing.authorSager, Hendrik B.en_US
dc.date.available2015-02-02T15:32:50Z
dc.identifier.doi10.1038/nm.3589*
dash.authorsorderedfalse
dash.contributor.affiliatedSager, Hendrik B
dash.contributor.affiliatedVinegoni, Claudio
dash.contributor.affiliatedDutta, Partha
dash.contributor.affiliatedLin, Charles
dash.contributor.affiliatedFricchione, Gregory
dash.contributor.affiliatedDenninger, John
dash.contributor.affiliatedCourties, Gabriel
dash.contributor.affiliatedSwirski, Filip
dash.contributor.affiliatedNahrendorf, Matthias
dash.contributor.affiliatedLibby, Peter
dash.contributor.affiliatedWeissleder, Ralph


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