Regulation of dendritic cell trafficking: a process that involves the participation of selective chemokines

DC function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leav e the tissues and move to the draining lymphoid organs where, converted int o mature DC, they prime naive T cells. This suggestive link between DC traf fic pattern and functions led to the investigation of the chemokine respons iveness of DC during their development and maturation. These studies have s hown that immature and mature DC are not recruited by the same chemokines. Immature DC respond to many CC- and CXC-chemokines (MIP-1 alpha, MIP-1 beta , MIP-5, MCP-3, MCP-4, RANTES, TECK, and SDF-1) and in particular to MIP-3 alpha/LARC, which acts through CCR6, a receptor mainly expressed in DC and lymphocytes, Like most other chemokines acting on immature DC, MIP-3 alpha is inducible on inflammatory stimuli. in contrast, mature DC have lost thei r responsiveness to most of these chemokines through receptor down-regulati on or desensitization, but acquired responsiveness to MIP-3 beta/ELC and 6C kine/SLC as a consequence of CCR7 up-regulation. MIP-3 alpha mRNA is only d etected within inflamed epithelial crypts of tonsils, the site of antigen e ntry known to be infiltrated by immature DC, whereas MIP-3 beta and 6Ckine are specifically expressed in the T cell-rich areas where mature IDC home. These observations suggest a role for chemokines induced on inflammation su ch as MIP-3 alpha in recruitment of immature DC at the site of injury and a role for MIP-3 beta/6Ckine in accumulation of antigen-loaded mature DC in T cell-rich areas of the draining lymph node. A better understanding of the regulation of DC trafficking might offer new opportunities of therapeutic interventions to suppress or stimulate the immune response.