title: Triggering of B7h by the ICOS modulates maturation and migration of monocyte-derived dendritic cells.
abstract: B7h, expressed by several cell types, binds ICOS expressed by activated T cells. We have previously shown that B7h triggering by ICOS-Fc inhibits human endothelial cell adhesiveness. This work investigated the effect of ICOS-Fc on human monocyte-derived dendritic cells (DCs). We found that DCs matured with LPS in the presence of ICOS-Fc (mDCs(ICOS)) produced greater amounts of IL-23 and IL-10, and promoted a higher secretion of IL-17A and IL-17F in MLCs than did those DCs matured with LPS alone (mDCs). Moreover, mDCs(ICOS) pulsed with the keyhole limpet hemocyanin Ag during the maturation phase were better stimulators of Ag-specific MHC class I-, but not class II-restricted T cells than mDCs. This was probably due to promotion of cross-presentation because it was not detected when the Flu-MA(58-66) Ag was directly loaded on already matured DCs and mDCs(ICOS). Finally, ICOS-Fc inhibited the adhesion of both immature DCs and mDCs to vascular and lymphoid endothelial cells, their migratory activity, and the expression of the Rac-1 activator β-Pix involved in cell motility. These data suggest that B7h stimulation modulates DC function with effects on their maturation and recruitment into tissues. This opens a novel view on the use of interactors of the ICOS:B7h system as immunomodulatory drugs.
authors.affiliation: Department of Medicine and Experimental Oncology, University of Torino, 10126 Torino, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Occhipinti
authors.forename: Chiara
authors.initials: C
authors.lastname: Dianzani
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiocchetti
authors.forename: Elena
authors.initials: E
authors.lastname: Boggio
authors.forename: Nausicaa
authors.initials: N
authors.lastname: Clemente
authors.forename: Casimiro Luca
authors.initials: CL
authors.lastname: Gigliotti
authors.forename: Maria Felicia
authors.initials: MF
authors.lastname: Soluri
authors.forename: Rosalba
authors.initials: R
authors.lastname: Minelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Fantozzi
authors.forename: Jungi
authors.initials: J
authors.lastname: Yagi
authors.forename: Josè Maria
authors.initials: JM
authors.lastname: Rojo
authors.forename: Daniele
authors.initials: D
authors.lastname: Sblattero
authors.forename: Mirella
authors.initials: M
authors.lastname: Giovarelli
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
mesh_terms: D017951:Antigen Presentation / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis / Q000235:genetics; D015789:HLA-A2 Antigen / Q000276:immunology; D006433:Hemocyanins / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000276:immunology*; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000166:cytology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C576606:ARHGEF7 protein, human; D020662:Guanine Nucleotide Exchange Factors; D015789:HLA-A2 Antigen; C556692:ICOS protein, human; C498514:ICOSLG protein, human; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; C482199:lipopolysaccharide, E coli O55-B5; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin