Circadian immunoregulation in cutaneous wound healing: from immune cell temporal heterogeneity to chronotherapeutic strategies

Cutaneous wound healing is not only a spatially coordinated reparative process but also a temporally organised immune programme shaped by circadian rhythms. This Review summarises how the central clock, peripheral clocks and core clock genes regulate time-dependent processes during skin repair, including immune cell recruitment, activation, resolution of inflammation and tissue remodelling. We focus on circadian regulation of neutrophil trafficking and effector functions, together with macrophage temporal heterogeneity and state transitions during inflammatory resolution. We further discuss the potential contributions of dendritic cells, mast cells, innate lymphoid cells and T cells to the temporal regulation of wound immunity. Circadian disruption associated with diabetes, ageing, sleep disturbance, obesity and aberrant light exposure may desynchronise immune responses, thereby promoting persistent inflammation, increased oxidative stress, heightened protease activity and enhanced formation of neutrophil extracellular traps, ultimately contributing to the development and progression of chronic non-healing wounds. Finally, we discuss chronotherapeutic strategies that align wound interventions, metabolic regulation, light exposure, sleep and feeding time with endogenous circadian rhythms. Incorporating circadian timing into wound-healing research may help redefine the temporal heterogeneity of immune cells and open new avenues for circadian-guided precision therapy for refractory chronic wounds.