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Role of Liver Circadian Rhythm in Adaptive Immunity

Circadian rhythms are 24‐hour biological cycles that coordinate sleep‐wake cycles, hormone secretion, body temperature, blood pressure, and liver metabolism. Disruption of circadian gene expression has been implicated in changes in metabolism, sleep:wakefulness, and immunity. Our study explores the role of circadian rhythm in the adaptive immune response. To address the hypothesis that circadian genes control adaptive immunity, wildtype mice were housed either in 12:12 light dark cyles (LD) or in complete darkness (DD) for 28 days to disrupt normal circadian cycles. Mice were then challenged with ConA (15mg/kg, intraperitoneal) at CT16 (16 hours post the onset of running bouts) and sacrificed 9 hours after ConA exposure. Serum ALT, innate cytokines (TNF, TGF) and T helper 1 cytokines (gINF) expression were significantly increased by ConA in wildtype mice housed in LD but blunted in mice housed in DD. However, T helper 2 (IL4, IL13) were significantly increased in DD housed mice compared to LD housed mice. Mice deficient in circadian regulator per2 were also resistant to ConA induced liver injury. These data suggest that adaptive immunity is indeed regulated by circadian control. Ongoing experiments will address the precise role of circadian genes such as per2 in the regulation of adaptive immune cells. This work was supported by NIAAA 1R15AA019559.