Circadian rhythm regulates immune cell function and participates in the development and progression of metabolic diseases

The circadian rhythm is an intrinsic ~24-hour timing system that plays a crucial role in regulating immune functions and maintaining metabolic homeostasis. This review provides a comprehensive overview of how the circadian clock influences five key immune cell types—macrophages, dendritic cells, B cells, T cells, and natural killer cells—affecting processes such as phagocytosis, antigen presentation, cytokine secretion, cell migration, antibody production, and cytotoxicity, along with their underlying molecular mechanisms. This review also examines the effects of circadian disruption on metabolic disorders—including obesity, insulin resistance/type 2 diabetes, and atherosclerosis—mediated by immune cell pathways. Key mechanisms include adipose tissue macrophage polarization, rhythmic IL-17A secretion by γδ T cells, and the temporal regulation of the Th17/Treg cell balance. Additionally, we address current challenges in fully elucidating these mechanisms and translating them into clinical applications, emphasizing promising avenues such as multi-omics integration, biomarker identification, and chrono-immunotherapy, while noting that the latter remains supported primarily by retrospective and hypothesis-generating evidence. Overall, this review seeks to provide a comprehensive framework for the emerging field of circadian immunometabolism and to facilitate the development of time-based precision strategies for managing metabolic diseases.