Abstract
The circadian clock enables organisms to predict daily environmental changes and synchronise their physiology and behaviour accordingly. Macrophages, key sensor cells in the innate immune system, exhibit cell-autonomous circadian rhythmicity. This circadian rhythmic behaviour is synchronised to the central clock in the hypothalamus as a result of neural, and hormonal signals. Macrophage rhythms and responses involve sensing temporal cues, integrating information from tissue-specific environments, and initiating context-appropriate, time-gated responses. On a broader scale, monocytes and macrophages communicate and synchronise with other immune cells, migrate throughout the body, and infiltrate tissues, collectively contributing to circadian regulation in both health and disease. While the field of macrophage circadian biology is rapidly advancing, it is equally important to reflect on its historical development, which has been shaped by over two centuries of accumulating knowledge and technological progress. This review traces key milestones in macrophage and circadian research, examining how recent discoveries have refined our understanding of early foundational questions and setting the stage for future inquiries. Notably, many intriguing questions remain unresolved, including the circadian regulation of macrophage function under steady-state conditions, the tissue-specific heterogeneity of macrophage circadian rhythms, and the role of macrophage circadian clocks in disease pathogenesis and their potential clinical implications.