Mirakaj, ValbonaDalli, Jesmond PGranja, TiagoRosenberger, PeterSerhan, Charles2015-01-052014Mirakaj, Valbona, Jesmond Dalli, Tiago Granja, Peter Rosenberger, and Charles N. Serhan. 2014. “Vagus nerve controls resolution and pro-resolving mediators of inflammation.” The Journal of Experimental Medicine 211 (6): 1037-1048. doi:10.1084/jem.20132103. http://dx.doi.org/10.1084/jem.20132103.0022-1007http://nrs.harvard.edu/urn-3:HUL.InstRepos:13581152Resolution of inflammation is now recognized as a biosynthetically active process involving pro-resolving mediators. Here, we show in zymosan-initiated peritoneal inflammation that the vagus nerve regulates local expression of netrin-1, an axonal guidance molecule that activates resolution, and that vagotomy reduced local pro-resolving mediators, thereby delaying resolution. In netrin-1+/− mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1+/+. Netrin-1 shortened the resolution interval, decreasing exudate neutrophils, reducing proinflammatory mediators, and stimulating the production of resolvins, protectins, and lipoxins. Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins. Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other’s expression and enhanced efferocytosis. These results indicate that the vagus nerve regulates both netrin-1 and pro-resolving lipid mediators, which act in a bidirectional fashion to stimulate resolution, and provide evidence for a novel mechanism for local neuronal control of resolution.en-USJournal Article2015-01-0510.1084/jem.20132103