Circadian rhythm regulates various aspect of physiological response in the single cell as well as behavior of an individual. Period 2 (Per2) gene is a member of circadian clock genes regulating mammalian circadian rhythm. Recent studies have reported that circadian rhythm disruption is associated with increased complication of inflammatory bowel disease. However, the underlying mechanism is unclear how circadian clock genes affect intestinal inflammation. In this study, we investigated whether unregulated circadian clock in absence of Per2 affects inflammatory response using chemically induced colitis. Per2 knockout (KO) mice were more susceptible to DSS-induced colitis than heterozygote littermates when the mice were monitored by change of body weights, disease activity score, and survival rates. Colon and mesenteric lymph nodes were analyzed for inflammatory cytokines, regulatory T cells, monocytes and neutrophils. Even though regulatory T cells were not impaired under steady state, regulatory T cells in MLN and colon, and inflammatory cytokines, especially TNF-alpha and IL-6, were up-regulated in colon of Per2KO mice under inflammatory condition. Per2KO mice showed decreased monocytes populations, but neutrophils were accumulated. The accumulation of neutrophils could be due to increased IL-17-producing CD4+ T cells in the lamina propria of Per2KO mice under steady state. These results suggested that unregulated circadian clock in absence of Per2 enhanced inflammatory tone against microbial stimuli in the colon.
