Circadian and sympathetic regulation of intestinal eosinophil abundance in mice

Eosinophils are abundant residents of the mouse small intestine under steady-state conditions. Their survival depends on the local cytokine milieu, including GM-CSF, and these cells contribute to the generation of IgA⁺ plasma cells. Here, we demonstrate that the abundance of small-intestinal eosinophils exhibits time-of-day variation accompanied by rhythmic GM-CSF expression. These oscillations were abolished in Clock-mutant mice, under disrupted light/dark cycles, and following pharmacological blockade of sympathetic nerve activity. Fecal IgA levels displayed similar temporal variation, which was likewise lost under these conditions. Together, these findings suggest that the circadian clock, potentially through sympathetic regulation of GM-CSF, helps coordinate eosinophil homeostasis and IgA production in the mouse small intestine.