Department of Epidemiology, Atherothrombosis and Imaging, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.
Cell. 2013 May 23;153(5):1025-35. doi: 10.1016/j.cell.2013.04.040.
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. PAPERFLICK:
在白细胞中，中性粒细胞具有独特的特点，它们会周期性地从骨髓中释放出来并迁移回骨髓中，然后在骨髓中被清除。由于清除死亡细胞会产生体内平衡信号，因此我们探讨了中性粒细胞的清除是否会在稳态下引发昼夜节律事件。在这里，我们报告称，中性粒细胞的稳态清除提供了调节骨髓生理学的线索。我们发现了一群在循环中“衰老”的 CD62L(LO)CXCR4(HI)中性粒细胞，它们在小鼠的休息期结束时被清除。衰老的中性粒细胞渗透到骨髓中，并促进造血龛的大小和功能减小。龛的调节取决于巨噬细胞和胆固醇感应核受体的激活，这对于造血祖细胞有节奏地进入循环是必不可少的。我们的研究结果揭示了一个同步免疫和造血节律的过程，并扩展了中性粒细胞除炎症以外的功能。
