Circadian Clock Regulation of Macrophage Functions

Macrophages mediate circadian regulation of systemic inflammation. At the molecular level, macrophage functions are directly governed by the circadian clock, and thus the circadian misalignment remodels the phenotype of macrophages from a ‘protective’ mode toward a ‘killer’ mode. Importantly, the pro-inflammatory macrophages induce systemic and chronic inflammation, leading to the development of a wide range of chronic diseases and the dampened immune defensive machinery against infectious diseases such as COVID-19. The development of inflammatory and infectious diseases as well as cancer, metabolic diseases, cardiovascular diseases, and the acceleration of aging, is exacerbated under chronic circadian rhythm misalignment through the functional remodeling of immune cells, including macrophages. Accumulating evidence unveils the molecular mechanisms underlying the circadian clock regulation of macrophage functions and the role of circadian rhythms in the development of inflammatory and infectious diseases. This chapter aims to summarize the latest insights from circadian regulation of macrophage functions and discuss the potential implications of circadian system-targeting macrophage rejuvenation.