Migration of dendritic cells into the lymphatics: the Langerhans cell example

Dendritic cells, including Langerhans cells of the epidermis and the mucous membranes, are key leukocytes for the initiation of adaptive immune responses as well as for the maintenance of peripheral tolerance. In the former regard they may well play an important, but as yet unrecognized role in the pathogenesis of Behçet's disease. Epidermal Langerhans cells may serve as a paradigm for their counterparts in the mucosae. These cells efficiently take up (microbial) antigens, they process them into immunogenic MHC–peptide complexes, and they transport this form of antigen to the lymph nodes via lymphatic vessels. Depending on the milieu where Langerhans cells have encountered antigen (inflammatory versus non-inflammatory/steady-state), they make T cells proliferate and acquire effector functions (immunity) or render them unresponsive or even delete them (tolerance), respectively. In addition, plasmacytoid dendritic cells, a recently characterized type of dendritic cells, may also directly trigger innate responses (e.g. by secretion of type I interferons in response to virus). Studying the pathways and the regulation of dendritic cell migration might help to unravel a possible involvement of dendritic cells in Behçet's disease.

We present observations on the physical obstacles that dendritic cells migrating in the skin have to overcome until they reach dermal lymphatic vessels. Furthermore, we show that migration is critically dependent on the function of matrix metalloproteinases, in particular MMP-2 and MMP-9. It becomes evident that Langerhans cells indeed carry antigens (including self antigens such as melanosomes or apoptotoic bodies or tumor antigens such as particular cytokeratins) through the lymphatics. Given these observations it may be worth studying Langerhans cells and dermal dendritic cells in Behçet's disease.