Glia-mediated gut-brain cytokine signaling couples sleep to intestinal inflammatory responses induced by oxidative stress.

ABSTRACT: Sickness-induced sleep is a behavior conserved across species that promotes recovery from illness, yet the underlying mechanisms are poorly understood. Here, we show that interleukin-6-like cytokine signaling from the Drosophila gut to brain glial cells regulates sleep. Under healthy conditions, this pathway promotes wakefulness. However, elevated gut cytokine signaling in response to oxidative stress - triggered by immune and inflammatory responses in the intestine - induces sleep. The cytokines Unpaired 2 and -3 are upregulated by oxidative stress in enteroendocrine cells and activate JAK-STAT signaling in glial cells, including those of the blood-brain barrier (BBB). This activity maintains elevated sleep during oxidative-stress-induced intestinal disturbances, suggesting that th

SUBMITTER: Malita A 

PROVIDER: S-EPMC12419797 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature