A temporal dialogue between the circadian clock and chronic inflammatory diseases.
Chen S., Ray D.
The circadian clock is an intrinsic molecular system that synchronises biological processes with daily environmental cycles. Under physiological conditions, cell-intrinsic clocks and systemic cues together regulate the circadian rhythmicity of immune activity, limiting immune responses to the appropriate time and intensity for optimal energy allocation and fitness. In chronic inflammation, by contrast, persistent and profound circadian alterations may cause a pro-inflammatory shift of homeostasis and hinder resolution. Circadian-based therapeutic strategies are emerging as promising approaches to overcome the limitations of conventional anti-inflammatory therapeutics and relieve treatment burden. This Review examines the bi-directional relationship between circadian regulation and chronic inflammation across immune-mediated, metabolic and infectious conditions. Circadian rhythms shape the timing, severity and tissue specificity of inflammatory responses, while inflammatory signals from diverse pathological settings converge on shared transcriptional nodes that interface with the clock, altering temporal organisation across multiple systems. We further highlight key future directions, including defining the molecular links between the circadian clock, inflammation and metabolism for precise target identification, restoring the intrinsic capacity for temporal homeostatic regulation through personalised circadian medicine, and integrating behavioural and environmental factors into the current framework. Together, they represent a path towards more precise, preventive and holistic management of chronic inflammatory diseases.