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.
