title: CD38 is expressed on human mature monocyte-derived dendritic cells and is functionally involved in CD83 expression and IL-12 induction.
abstract: Dendritic cell (DC) maturation is characterized by the gain or loss of immunological functions and by expression of distinctive surface receptors. CD38 is an ectoenzyme that catalyzes the synthesis of cyclic ADP ribose (a potent second messenger for Ca(2+) release), as well as a receptor that initiates transmembrane signaling upon engagement with its counter-receptor CD31 or with agonistic monoclonal antibodies. Since CD38 is expressed by resting monocytes, we aimed to monitor CD38 expression during the differentiation of human monocyte-derived DC (MDDC) and to investigate the possibility that CD38 plays a functional role during DC maturation. CD38 is down-modulated during differentiation into immature MDDC and expressed again upon maturation. The extent of CD38 expression is dependent on the stimulus adopted (LPS > IFN-gamma > CD40 cross-linking). Although weak, IFN-gamma consistently induces DC maturation. De novo-synthesized CD38 is enzymatically active, and its expression in mature (m) MDDC is dependent on NF-kappa B activity. However, CD38 is not merely a maturation marker but also mediates signaling in mMDDC, where it maintains its functions as a receptor. Activation via agonistic anti-CD38 mAb induces up-regulation of CD83 expression and IL-12 secretion, whereas disruption of CD38/CD31 interaction inhibits CD83 expression, IL-12 secretion and MDDC-induced allogeneic T cell proliferation.
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fedele
authors.forename: Loredana
authors.initials: L
authors.lastname: Frasca
authors.forename: Raffaella
authors.initials: R
authors.lastname: Palazzo
authors.forename: Enza
authors.initials: E
authors.lastname: Ferrero
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Clara Maria
authors.initials: CM
authors.lastname: Ausiello
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000378:metabolism*; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011946:Receptors, Antigen / Q000378:metabolism; D000097802:CD83 Antigen
chemical_list: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D007136:Immunoglobulins; D018664:Interleukin-12; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011946:Receptors, Antigen; D000097802:CD83 Antigen; C498154:CD38 protein, human