Research Article

Circadian Gene Bmal1 Regulates Diurnal Oscillations of Ly6Chi Inflammatory Monocytes

Science  27 Sep 2013:
Vol. 341, Issue 6153, pp. 1483-1488
DOI: 10.1126/science.1240636

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Diurnal Immunology

Like most organ systems in the body, several components of the immune system appear to be regulated in a diurnal manner. However, the cell populations affected, the underlying molecular mechanisms controlling these processes, and the functional consequences of such regulation are poorly understood. Now, Nguyen et al. (p. 1483, published online 22 August; see the Perspective by Druzd and Scheiermann) have found that trafficking of monocytes to sites of inflammation is regulated in a diurnal manner in mice. Mice harboring a myeloid cell-specific deletion in the clock protein, BMAL1, showed reduced fitness in response to both acute and chronic inflammation.

Abstract

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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