The oral immune and inflammatory network under circadian clock control

Circadian rhythms are essential regulators of immune homeostasis, coordinating immune cell functions, inflammatory responses, and tissue repair. Although extensive studies have revealed the importance of circadian regulation in systemic immunity, most mechanistic insights are derived from peripheral immune systems and non-oral tissues. The oral cavity is a unique immune interface continuously exposed to complex microbial communities; however, the role of circadian regulation in oral immune homeostasis and disease development remains poorly understood. This review summarizes the mechanisms by which circadian clocks regulate oral immunity, focusing on immune cell functions, inflammatory responsiveness, tissue homeostasis, and interactions between circadian clock components and inflammatory signaling networks. We further discuss the emerging temporal dynamics of the oral microbiome and the potential effects of host circadian rhythms, feeding schedules, and chrono-nutrition on microbial ecology and immune balance. Current evidence linking circadian disruption with oral diseases, including periodontitis, dental caries, apical periodontitis, Sjögren's syndrome, temporomandibular joint inflammatory disorders, and oral squamous cell carcinoma, is also reviewed, with emphasis on distinguishing direct oral evidence from extrapolated mechanisms. Finally, we highlight circadian-based therapeutic strategies and existing limitations, underscoring the need for longitudinal studies, multi-omics approaches, and personalized circadian interventions in oral medicine.