Circadian control of duodenal regulatory T cells by enteric neurons and eosinophils

Multiple intestinal functions including nutrient absorption and peristalsis display regional specialization as well as time-of-day effect under the control of circadian rhythm. We investigated the role of these adaptations on intestinal immune system and response to dietary antigens. We found that oral challenge during the night resulted in more protective tolerance, which correlated with nocturnal expansion of regulatory T (Treg) cells in proximal small intestine lamina propria. Expansion of Treg cells was supported by eosinophils and clock gene-dependent rhythmic production of follistatin by enteric neurons. Circadian entrainment of these changes depended on light exposure and locomotor activity but not the time of food intake. These data suggest that circadian and regional adaptations in the intestine limit the severity of allergic reactions during the active phase. Overall design: CD11c-high and CD11c-low duodenum lamina propria eosinophils were sorted for RNAseq at ZT3 (AM) and ZT15 (PM)