Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Immunity. 2023 Apr 11;56(4):783-796.e7. doi: 10.1016/j.immuni.2023.01.024. Epub 2023 Feb 23.
Diet profoundly influences physiology. Whereas over-nutrition elevates risk for disease via its influence on immunity and metabolism, caloric restriction and fasting appear to be salutogenic. Despite multiple correlations observed between diet and health, the underlying biology remains unclear. Here, we identified a fasting-induced switch in leukocyte migration that prolongs monocyte lifespan and alters susceptibility to disease in mice. We show that fasting during the active phase induced the rapid return of monocytes from the blood to the bone marrow. Monocyte re-entry was orchestrated by hypothalamic-pituitary-adrenal (HPA) axis-dependent release of corticosterone, which augmented the CXCR4 chemokine receptor. Although the marrow is a safe haven for monocytes during nutrient scarcity, re-feeding prompted mobilization culminating in monocytosis of chronologically older and transcriptionally distinct monocytes. These shifts altered response to infection. Our study shows that diet-in particular, a diet's temporal dynamic balance-modulates monocyte lifespan with consequences for adaptation to external stressors.
饮食对生理机能有深远影响。营养过剩会通过影响免疫和代谢而增加患病风险，而热量限制和禁食似乎对健康有益。尽管饮食与健康之间存在多种关联，但潜在的生物学机制仍不清楚。在这里，我们发现了白细胞迁移的一种由禁食诱导的开关，它延长了单核细胞的寿命，并改变了小鼠对疾病的易感性。我们表明，在活跃期禁食会促使单核细胞从血液快速返回骨髓。单核细胞的重新进入是由下丘脑-垂体-肾上腺 (HPA) 轴依赖的皮质酮释放来协调的，皮质酮增加了趋化因子受体 CXCR4。尽管骨髓在营养匮乏期间是单核细胞的安全避难所，但重新进食会促使动员，最终导致单核细胞增多，其中包括年龄更大和转录上不同的单核细胞。这些变化改变了对感染的反应。我们的研究表明，饮食——尤其是饮食的时间动态平衡——调节单核细胞的寿命，从而对适应外部应激产生影响。
