Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory monocytes.

Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory monocytes.
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DOI:
10.1126/science.1240636
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发表时间:
2013-09-27
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Chawla A
Chawla A
中科院分区:
其他
文献类型:
--
作者:
Nguyen KD;Fentress SJ;Qiu Y;Yun K;Cox JS;Chawla A

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生物钟已经进化到在预期环境变化的情况下调节生理和行为节律。虽然分子钟存在于先天免疫细胞中,但其在单核细胞稳态中的作用仍然未知。在这里,我们报告说,Ly6Chi炎性单核细胞表现出昼夜变化,这控制了他们的运输到炎症部位。这种循环模式的运输赋予保护对单核细胞增多性李斯特菌和调节的抑制活性的昼夜节律基因BMAL1。因此,骨髓细胞特异性缺失BMAL1诱导单核细胞吸引趋化因子的表达,并破坏Ly6Chi单核细胞的节律性循环,使小鼠易于发展与急性和慢性炎症相关的病理学。这些发现揭示了BMAL1在控制Ly6Chi单核细胞数量的昼夜节律中的关键作用。
Circadian clocks have evolved to regulate physiologic and behavioral rhythms in anticipation of changes in the environment. Although the molecular clock is present in innate immune cells, its role in monocyte homeostasis remains unknown. Here, we report that Ly6Chi inflammatory monocytes exhibit diurnal variation, which controls their trafficking to sites of inflammation. This cyclic pattern of trafficking confers protection against Listeria monocytogenes and is regulated by the repressive activity of the circadian gene BMAL1. Accordingly, myeloid cell-specific deletion of BMAL1 induces expression of monocyte-attracting chemokines and disrupts rhythmic cycling of Ly6Chi monocytes, predisposing mice to development of pathologies associated with acute and chronic inflammation. These findings have unveiled a critical role for BMAL1 in controlling the diurnal rhythms in Ly6Chi monocyte numbers.
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