Immunity's fourth dimension: approaching the circadian–immune connection

The circadian system ensures the generation and maintenance of self-sustained ∼24-h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related disease. Here, we discuss the molecular links between the circadian and immune systems and examine their outputs and disease implications. Understanding the mechanisms that underlie circadian–immune crosstalk may prove valuable for devising novel prophylactic and therapeutic interventions.