Innate Rhythms: Clocks at the Center of Monocyte and Macrophage Function

Abstract

The circadian cycle allows organisms to track external time of day and predict/respond to changes in the external environment. In higher order organisms, circadian rhythmicity is a central feature of innate and adaptive immunity. We focus on the role of the molecular clock and circadian rhythmicity specifically in monocytes and macrophages of the innate immune system. These cells display rhythmicity in their internal functions, such as metabolism and inflammatory mediator production as well as their external functions in pathogen sensing, phagocytosis, and migration. These inflammatory mediators are of clinical interest as many are therapeutic targets in inflammatory disease such as cardiovascular disease, diabetes, and rheumatoid arthritis. Moreover, circadian rhythm disruption is closely linked with increased prevalence of these conditions. Therefore, understanding the mechanisms by which circadian disruption affects monocyte/macrophage function will provide insights into novel therapeutic opportunities for these chronic inflammatory diseases.

Keywords: cell migration; circadian; immunometabolism; inflammation; macrophage; molecular clock; monocyte; phagocytosis.

Figure 1

(A) The molecular clock transcription factor feedback loop. (B) Peaks troughs in murine monocyte and macrophage inflammatory mediators across the 24 h day.

Figure 2

Circadian clock proteins mediated molecular regulation of (A) chemokines and (B) cytokines.