FIG. 1.

Dendritic cell (DC) migration into afferent lymphatic vessels (LVs). (A) In tissues like the skin LVs begin as blind-ended capillaries, which merge into collecting vessels and connect with dLNs. DC migration into afferent LVs primarily occurs at the level of CCL21-expressing lymphatic capillaries. In contrast to lymphatic collectors, lymphatic capillaries have a highly fenestrated basement membrane and are not surrounded by smooth muscle cells (SMCs). (B) While lymphatic endothelial cells (LECs) in lymphatic collectors are tightly connected by continuous, “zipper-like” cell junctions (solid black lines), lymphatic capillaries display a discontinuous, “button-like” expression of junctional adhesion molecules (dotted black lines). (C) In lymphatic capillaries, adjacent oakleaf-shaped LECs partially overlap, thereby creating open flaps. DCs are thought to transmigrate the lymphatic endothelium by migrating through the flaps (black lines). Red lines represent tight and adherens junctions present between neighboring LECs. (D) The chemokine CCL21 is constitutively expressed by lymphatic vessels and attracts CCR7-expressing DCs. The expression of LYVE-1 (green) and CCL21 (red) was analyzed in tissue whole mounts prepared from murine ear skin. Stainings were performed under PFA-fixed and permeabilizing conditions, as described.⁶⁶ CCL21 is mainly present in intracellular deposits in LECs. Scale bar: 200 μm.