As an evolutionarily conserved timekeeping system, the circadian clock orchestrates physiological adaptations to diurnal environmental cues through transcriptional-translational feedback loops (TTFLs). Accumulating evidence reveals that circadian regulation governs immunological processes, with the immune system—a critical host defense mechanism—exhibiting robust circadian rhythmicity in functional organization. This review synthesizes recent advances in circadian modulation of pathogen-host interactions, immune cell trafficking, effector functions, circadian light hygiene—gut immune crosstalk, and tumor immunobiology. We examine the bidirectional crosstalk between circadian oscillators and immune pathways while addressing the clinical implications for immune-related pathologies. Significantly, we advocate chrono-immunotherapy as a transformative paradigm that leverages circadian principles to optimize therapeutic timing, enhancing efficacy while minimizing adverse effects. Future research directions aimed at elucidating mechanistic foundations and accelerating clinical translation are outlined. A comprehensive understanding of circadian-immune system dynamics not only provides fundamental insights into biological regulation but also establishes a chronobiological framework for precision medicine in immune-mediated disorders.
Jiang et al. (2025) studied this question.