Inflammation, lymphatic function, and dendritic cell migration.

The lymphatic system is not only essential for maintenance of normal fluid balance, but also for proper immunologic function by providing an extensive network of vessels, important for cell trafficking and antigen delivery, as well as an exclusive environment, the lymph node (LN), where antigen-presenting cells (APCs) and lymphocytes can encounter and interact. Among APCs, dendritic cells (DCs) have a remarkable capacity to traffic from peripheral tissues to the draining LN, which is critical for execution of their functions. To reach the LN, DCs must migrate towards and enter lymphatic vessels. Here, the authors review what is known about the factors that drive this process. They touch particularly on the topic of how DC migration is affected by inflammation and discuss this in the context of lymphatic function. Traditionally, inflammatory mediators are regarded to support DC migration to LNs because they induce molecules on DCs known to guide them to lymphatics. The authors recently showed that inflammatory signals present in a strong vaccine adjuvant induce swelling in LNs accompanied by lymphangiogenesis in the draining LN and radius of peripheral tissue. These increased lymphatics, at least for several days, lead to a more robust migration of DCs. However, the density of lymphatic vessels can become overly extended and/or their function impaired as observed during lymphedema and various chronic inflammatory reactions. Diseases characterized by chronic inflammation often present with impaired DC migration and adaptive immunity. Gaining a better understanding of how lymphatic vessel function may impact adaptive immunity by, for example, altering DC migration will benefit clinical research aiming to manipulate immune responses and manage chronic inflammatory diseases.