DC-SIGN mediates adhesion and rolling of dendritic cells on primary human umbilical vein endothelial cells through LewisY antigen expressed on ICAM-2.
Immature dendritic cells (DCs) are recruited from blood into tissues to patrol for foreign antigens. After antigen uptake and processing, DCs mature and migrate to the secondary lymphoid organs where they initiate immune responses. DC-SIGN is a DC-specific C-type lectin that acts both as a pattern recognition receptor and as an adhesion molecule. As an adhesion molecule, DC-SIGN is able to mediate rolling and adhesion over endothelial cells under shear flow. In this study, we show that the binding partner of DC-SIGN on endothelial cells is the glycan epitope Lewis(Y) (Le(Y)), expressed on ICAM-2. The interaction between DC-SIGN on dendritic cells and ICAM-2 on endothelial cells is strictly glycan-specific. ICAM-2 expressed on CHO cells only served as a ligand for DC-SIGN when properly glycosylated, underscoring its function as a scaffolding protein. The expression of Le(Y) in endothelial cells is directed by the enzyme FUT1. Silencing of FUT1 results in a decrease in the rolling and adhesion of immature DCs over endothelial cells. The identification of Le(Y) as the carbohydrate ligand of DC-SIGN in endothelial cells opens new possibilities for the manipulation of DC migration.
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D016466:CHO Cells; D050260:Carbohydrate Metabolism / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D000939:Epitopes; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D007983:Lewis Blood Group Antigens / Q000276:immunology*; D016256:Lewis X Antigen; D008024:Ligands; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000276:immunology*; D014471:Umbilical Veins / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D000097631:Galactoside 2-alpha-L-fucosyltransferase; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D003208:Concanavalin A; D000939:Epitopes; D005647:Fucosyltransferases; D037181:Lectins, C-Type; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D008024:Ligands; D011956:Receptors, Cell Surface; D000097631:Galactoside 2-alpha-L-fucosyltransferase; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C065289:ICAM2 protein, human; C094162:Lewis Y antigen; C066693:FUT4 protein, human