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

Science. 2013 Sep 27;341(6153):1483-8. doi: 10.1126/science.1240636. Epub 2013 Aug 22.

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 Ly6C(hi) 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 Ly6C(hi) 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 Ly6C(hi) monocyte numbers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • ARNTL Transcription Factors / metabolism*
  • Animals
  • Antigens, Ly / immunology
  • Chemokines / genetics
  • Chemotaxis / genetics
  • Chemotaxis / immunology
  • Circadian Clocks / genetics
  • Circadian Clocks / immunology*
  • Circadian Rhythm / genetics
  • Circadian Rhythm / immunology*
  • Gene Expression Regulation
  • Inflammation / genetics
  • Inflammation / immunology*
  • Listeria monocytogenes / immunology
  • Listeria monocytogenes / pathogenicity
  • Listeriosis / genetics
  • Listeriosis / immunology
  • Metabolic Diseases / metabolism
  • Mice
  • Mice, Knockout
  • Monocytes / immunology*
  • Myeloid Cells / metabolism

Substances

  • ARNTL Transcription Factors
  • Antigens, Ly
  • Arntl protein, mouse
  • Chemokines
  • Ly-6C antigen, mouse