title: CC-chemokine ligand 16 induces a novel maturation program in human immature monocyte-derived dendritic cells.
abstract: Dendritic cells (DCs) are indispensable for initiation of primary T cell responses and a host's defense against infection. Many proinflammatory stimuli induce DCs to mature (mDCs), but little is known about the ability of chemokines to modulate their maturation. In the present study, we report that CCL16 is a potent maturation factor for monocyte-derived DCs (MoDCs) through differential use of its four receptors and an indirect regulator of Th cell differentiation. MoDCs induced to mature by CCL16 are characterized by increased expression of CD80 and CD86, MHC class II molecules, and ex novo expression of CD83 and CCR7. They produce many chemokines to attract monocytes and T cells and are also strong stimulators in activating allogeneic T cells to skew toward Th1 differentiation. Interestingly, they are still able to take up Ag and express chemokine receptors usually bound by inflammatory ligands and can be induced to migrate to different sites where they capture Ags. Our findings indicate that induction of MoDC maturation is an important property of CCL16 and suggest that chemokines may not only organize the migration of MoDCs, but also directly regulate their ability to prime T cell responses.
authors.affiliation: Center for Experimental Research and Medical Studies, San Giovanni Battista Hospital, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cappello
authors.forename: Tiziana
authors.initials: T
authors.lastname: Fraone
authors.forename: Laura
authors.initials: L
authors.lastname: Barberis
authors.forename: Carlotta
authors.initials: C
authors.lastname: Costa
authors.forename: Emilio
authors.initials: E
authors.lastname: Hirsch
authors.forename: Angela R
authors.initials: AR
authors.lastname: Elia
authors.forename: Cristiana
authors.initials: C
authors.lastname: Caorsi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Musso
authors.forename: Francesco
authors.initials: F
authors.lastname: Novelli
authors.forename: Mirella
authors.initials: M
authors.lastname: Giovarelli
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D002454:Cell Differentiation; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000494:pharmacology* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; C481939:CCL16 protein, human; C515370:CCR7 protein, human; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D054400:Receptors, CCR7; D019707:Receptors, Chemokine