CD38 orchestrates migration, survival, and Th1 immune response of human mature dendritic cells.
CD38, an ectoenzyme and a signaling receptor, is a novel marker of human mature monocyte-derived dendritic cells (MDDCs). The working hypothesis is that CD38 is not only a marker but also contributes to functions specifically gained by MDDCs with maturation. This was tested by assessing the role(s) of CD38 after signaling with agonistic anti-CD38 monoclonal antibodies or by blocking the interactions taking place between CD38 and CD31, its counterreceptor. The results indicate the following: (1) CD38 engagement in MDDCs ensures efficient chemotaxis and transendothelial migration driven by CC chemokine ligand 21 (CCL21); (2) CD38 is laterally associated with the CCL21-specific CC chemokine receptor 7 and with CD83 and CD11b; (3) CD38 localizes in membrane lipid domains; (4) CD38 signaling contributes to support longevity of lipopolysaccharide (LPS)-matured MDDCs after growth factor withdrawal; and (5) IFN-gamma is produced by cocultured T lymphocytes, thus affecting T-helper 1 (Th1) polarization. These data suggest that the localization of CD38 in lipid rafts and its multiple interactions with signaling receptors rule innate and adaptive immune responses by tuning DC migration, survival, and Th1-polarization ability. These findings may lay out the basis to assess the functional role(s) of human CD38 in infections, autoimmune diseases, and neoplastic disorders.
Frasca
Loredana
L
Department of Infectious, Parasitic, and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Fedele
Giorgio
G
Deaglio
Silvia
S
Capuano
Cristina
C
Palazzo
Raffaella
R
Vaisitti
Tiziana
T
Malavasi
Fabio
F
Ausiello
Clara Maria
CM
D051997:ADP-ribosyl Cyclase 1 / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology*; D002460:Cell Line; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000502:physiology; D002633:Chemotaxis; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D007109:Immunity; D021962:Membrane Microdomains; D009000:Monocytes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology
C515478:CCL21 protein, human; D054421:Chemokine CCL21; D019742:Chemokines, CC; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051997:ADP-ribosyl Cyclase 1