Mechanism Behind Dendritic Cell Migration to Lymph Nodes Revealed

Research published recently in the Journal of Experimental Medicine, sheds light on how dendritic cells migrate from the body’s tissues into lymphatic vessels and from there to the lymph nodes. For a long time, scientists assumed that dendritic cells choose the path of least resistance and migrate from the tissue into the lymphatic capillaries, which are surrounded only by a thin, barely closed layer of cells, allowing dendritic cells to slip through the spaces between neighboring cells relatively easily.

However, according to the paper from ETH Zurich researchers, dendritic cells can take a shortcut. The team was able to show that dendritic cells can also migrate directly into those lymphatic vessels into which the capillaries merge: the collecting lymphatics. These vessels are surrounded by a well-sealed layer of cells and a thicker membrane of connective tissue. Consequently, migration across these barriers is more difficult for dendritic cells, and entry takes longer than into capillaries. All in all, however, dendritic cells taking this path arrive in the lymph nodes much faster, since immediately after entry they are carried along by the lymph flow present in the collecting vessels and can bypass the slow active migration step in the capillaries.

At present, it is not yet completely understood under which circumstances dendritic cells choose the known path via the capillaries and under which they take the newly discovered shortcut. However, the team was able to show that the shortcut becomes available when there is an ongoing inflammatory response in the tissue. Specifically, the researchers were able to show that the connective tissue membrane surrounding the collecting lymphatics becomes degraded during inflammation, making it easier for dendritic cells to penetrate into the collectors.

It thus appears that an inflammatory response is the key factor that allows dendritic cells to take this shortcut and arrive more quickly in the lymph nodes. The scientists will now investigate whether all dendritic cells or only specific subtypes can travel via this route. In particular, they plan to explore the importance of the newly discovered pathway for the activation of the immune system and for installing immune responses. They suspect that the ability to sound the alarm in the lymph node more quickly may provide an advantage in fighting certain infections.