Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells
Exercise reduces inflammatory cell production and cardiovascular inflammation via instruction of hematopoietic progenitor cells
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DOI：
10.1038/s41591-019-0633-x
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发表时间：
2019-11-01
期刊：
影响因子：
82.9
通讯作者：
Nahrendorf, Matthias
中科院分区：
文献类型：
--
作者：
Frodermann, Vanessa;Rohde, David;Nahrendorf, Matthias
久坐不动的生活方式、慢性炎症和白细胞增多会增加动脉粥样硬化;然而，定期的体育活动是否会影响白细胞的产生仍不清楚。在这里，我们表明，自愿运行降低小鼠的造血活动。运动可以保护患有动脉粥样硬化的小鼠和人类免受慢性白细胞增多的影响，但不影响小鼠的紧急造血。从机制上讲，运动减少了脂肪组织中瘦素的产生，增加了瘦素受体阳性基质骨髓细胞中促进造血生态位因子的静止。在Prrx 1-creER（T2）; Lepr（fl/fl）小鼠中诱导的瘦素受体缺失揭示了瘦素对骨髓小生境细胞的作用调节造血干细胞和祖细胞（HSPC）增殖和白细胞产生，以及心血管炎症和结果。而跑步轮撤退迅速逆转瘦素水平，运动对白细胞产生和HSPC表观基因组和转录组的影响持续数周。总之，这些数据表明，身体活动通过调节HSPC的生态位来改变HSPC，从而减少炎性白细胞的造血输出。
A sedentary lifestyle, chronic inflammation and leukocytosis increase atherosclerosis; however, it remains unclear whether regular physical activity influences leukocyte production. Here we show that voluntary running decreases hematopoietic activity in mice. Exercise protects mice and humans with atherosclerosis from chronic leukocytosis but does not compromise emergency hematopoiesis in mice. Mechanistically, exercise diminishes leptin production in adipose tissue, augmenting quiescence-promoting hematopoietic niche factors in leptin-receptor-positive stromal bone marrow cells. Induced deletion of the leptin receptor in Prrx1-creER(T2); Lepr(fl/fl) mice reveals that leptin's effect on bone marrow niche cells regulates hematopoietic stem and progenitor cell (HSPC) proliferation and leukocyte production, as well as cardiovascular inflammation and outcomes. Whereas running wheel withdrawal quickly reverses leptin levels, the impact of exercise on leukocyte production and on the HSPC epigenome and transcriptome persists for several weeks. Together, these data show that physical activity alters HSPCs via modulation of their niche, reducing hematopoietic output of inflammatory leukocytes.