Fig. 6

β-adrenergic signaling in enteric glia triggers enteric glial reactivity and modulates intestinal inflammation in POI. A Graphical abstract of the longitudinal analysis of enteric glia after intestinal manipulation (IM) showing a distinct separation into three stages defined by specific hallmarks. Initial reaction (IM3h, magenta) includes an immediate inflammatory reaction and the shaping of the intestinal environment in concert with the initiation of cell migration (blue). This migratory phenotype manifests further 24 h after IM and is accompanied by elevated proliferation (light blue). Finally, inflammatory reactions of enteric glia continuously taper off and are gradually replaced by resolution-related genes (yellow) that initiate a return to the regular intestinal environment. B Graphical abstract of SNS activation of enteric glia. Skin incision and laparotomy (in the absence of IM) lead to immediate activation of the SNS, which triggers enteric glial reactivity in the small bowel ME. Sympathetic nerve endings in the ME release NE, which binds to adrenergic receptors β1 or β2 on myenteric enteric glia. Enteric glia subsequently become reactive (FOS, Stat3) and induce upregulation and release of inflammatory mediators (CCL2, IL-6) that in turn modulate immune cells. Chemical disruption of the sympathetic innervation reduces the reactive enteric glia phenotype and the postsurgical inflammatory response