Cutting edge: Peripheral neuropeptides attract immature and arrest mature blood-derived dendritic cells

Dendritic cells (DC) are highly motile and play a key rot in mediating immu ne responses in various tissues and lymphatic organs. We investigated locom otion of mononuclear cell-derived DC at different maturation stages toward gradients of sensory neuropeptides in vitro. Calcitonin gene-related peptid e, vasoactive intestinal polypeptide, secretin, and secretoneurin induced i mmature DC chemotaxis comparable to the potency of RANTES, whereas substanc e P and macrophage-inflammatory protein-3 beta stimulated immature cell mig ration only slightly, Checkerboard analyses revealed a true chemotactic res ponse induced by neuropeptides, Upon maturation of DC, neuropeptides inhibi ted spontaneous, macrophage-inflammatory protein-3 beta- and 6Ckine-induced cell migration. Maturation-dependent changes in migratory behavior coincid ed with distinct neuropeptide-induced signal transduction in DC. Peripheral neuropeptides might guide immature DC to peripheral nerve fibers where hig h concentrations of these peptides can arrest the meanwhile matured cells, It seems that one function of sensory nerves is to fasten DC at sites of in flammation.