Journal
CELL
Volume 153, Issue 5, Pages 1025-1035Publisher
CELL PRESS
DOI: 10.1016/j.cell.2013.04.040
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [WE1913/11-2, SFB914-B8, R01-DK056638, R01-HL69438, SAF2008-00057, SAF2011-29244]
- Ramon y Cajal Fellowship [RYC-2007-00697]
- MINECO [SAF2009-11037]
- Comunidad de Madrid [S2010/BMD-2314]
- FP7-People-IRG Program [246655]
- Human Frontiers in Science Program long-term fellowship [00194/2008]
- Spanish Ministry of Economy and Competitivity
- Pro-CNIC Foundation
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Unique among leukocytes, neutrophils follow daily cycles of release from and migration back into the bone marrow, where they are eliminated. Because removal of dying cells generates homeostatic signals, we explored whether neutrophil elimination triggers circadian events in the steady state. Here, we report that the homeostatic clearance of neutrophils provides cues that modulate the physiology of the bone marrow. We identify a population of CD62L(LO) CXCR4(HI) neutrophils that have aged'' in the circulation and are eliminated at the end of the resting period in mice. Aged neutrophils infiltrate the bone marrow and promote reductions in the size and function of the hematopoietic niche. Modulation of the niche depends on macrophages and activation of cholesterol-sensing nuclear receptors and is essential for the rhythmic egress of hematopoietic progenitors into the circulation. Our results unveil a process that synchronizes immune and hematopoietic rhythms and expand the ascribed functions of neutrophils beyond inflammation.
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