In situ demonstration of dendritic cell migration from rat intestine to mesenteric lymph nodes: relationships to maturation and role of chemokines

Dendritic cells (DCs) are continuously transported from the intestine to mesenteric lymph nodes (MLNs). The objective of this study was to determine the migration kinetics of DCs via intes- tinal lymph and to investigate regulatory factors affecting their migration in vivo. DCs were ob- tained from spleen or thoracic duct lymph of mes- enteric lymphadenectomized rats. The DCs were fluorescently labeled and injected into the subse- rosa of the small intestine near the cecum, and their migration patterns into MLNs were deter- mined. Isolated DCs from intestinal lymph express intercellular adhesion molecule-1 (ICAM-1), CD11b/c, CD80/86, and major histocompatibility complex class II but maintain their ability to phagocytize latex particles, suggesting the pres- ence of immature DCs. The isolated DCs accumu- lated in MLNs in a time-dependent manner with maximal accumulation at 48 h. Cytokine-induced maturation of lymph DCs did not cause a change in cell number but accelerated their transport into MLNs with a maximum at 24 h. Splenic DCs showed an intermediate level of maturation and a migration pattern similar to mature DCs. Inhibi- tion of ICAM-1 or CD11b/c did not affect DC migration. Migration of mature DCs to MLNs was specifically blocked by desensitization of CCR7 with CCL21. In contrast, freshly isolated lymph DCs were not chemotactic for CCL21, but their migration to MLNs was mainly inhibited by desen- sitization of CCR6 with CCL20. The migratory ability of DCs correlates well with their degree of maturation, and different chemokine/chemokine receptor use may be the main regulator of DC migration kinetics through intestinal lymph. J. Leu- koc. Biol. 75: 000-000; 2004.