XRhythmic modulation of the hematopoietic niche through neutrophil clearance

María Casanova-Acebes, Christophe Pitaval, Linnea A. Weiss, César Nombela-Arrieta, Raphaël Chèvre, Noelia A-González, Yuya Kunisaki, Dachuan Zhang, Nico Van Rooijen, Leslie E. Silberstein, Christian Weber, Takashi Nagasawa, Paul S. Frenette, Antonio Castrillo, Andrés Hidalgo

Research output: Contribution to journalArticlepeer-review

518 Scopus citations


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 CXCR4HI 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. PaperFlick

Original languageEnglish
Pages (from-to)1025
Number of pages1
Issue number5
StatePublished - 23 May 2013
Externally publishedYes


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