Dendritic cells (DCs) are recruited from blood into tissues to patrol for f
oreign antigens, After antigen uptake and processing, DCs migrate to the se
condary lymphoid organs to initiate immune responses. We now show that DC-S
IGN, a CC-specific C-type lectin, supports tethering and rolling of DC-SIGN
-positive cells on the vascular ligand ICAM-2 under shear flow, a prerequis
ite for emigration from blood. The DC-SIGN-ICAM-2 interaction regulates che
mokine-induced transmigration of DCs across both resting and activated endo
thelium. Thus, DC-SIGN is central to the unusual trafficking capacity of DC
s, further supported by the expression of DC-SIGN on precursors in blood an
d on immature and mature DCs in both peripheral and lymphoid tissues.