title: Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells.
abstract: Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1(+) DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1(+) human DC. Assessment of the immunoactivation potential of XCR1(+) human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1(+) and XCR1(-) human DC in CD34(+) progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR1(-) CD34-DC are similar to canonical MoDC, whereas XCR1(+) CD34-DC resemble XCR1(+) blood DC (bDC). XCR1(+) DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1(+) DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1(+) CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1(+) bDC. Hence, it is feasible to generate high numbers of bona fide XCR1(+) human DC in vitro as a model to decipher the functions of XCR1(+) bDC and as a potential source of XCR1(+) DC for clinical use.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France; INSERM, Unité Mixte de Recherche 1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille, France;
authors.forename: Sreekumar
authors.initials: S
authors.lastname: Balan
authors.affiliation: Institut des Sciences Pharmaceutiques et Biologiques, Université Lyon 1, Université de Lyon, 69373 Lyon, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5286, Département Immunité, Virus et Microenvironnement, Centre de Recherche en Cancérologie de Lyon, 69373 Lyon, France; INSERM U1052, Centre Léon Bérard, 69373 Lyon, France; LabEx DEVweCAN, 69373 Lyon, France;
authors.forename: Vincent
authors.initials: V
authors.lastname: Ollion
authors.affiliation: Sanofi, Cambridge, MA 02139;
authors.forename: Nicholas
authors.initials: N
authors.lastname: Colletti
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France; INSERM, Unité Mixte de Recherche 1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille, France;
authors.forename: Rabie
authors.initials: R
authors.lastname: Chelbi
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France; INSERM, Unité Mixte de Recherche 1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille, France;
authors.forename: Frédéric
authors.initials: F
authors.lastname: Montanana-Sanchis
authors.affiliation: Sanofi, Cambridge, MA 02139;
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France; INSERM, Unité Mixte de Recherche 1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille, France;
authors.forename: Thien-Phong
authors.initials: TP
authors.lastname: Vu Manh
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France; INSERM, Unité Mixte de Recherche 1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille, France;
authors.forename: Cindy
authors.initials: C
authors.lastname: Sanchez
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France; INSERM, Unité Mixte de Recherche 1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille, France;
authors.forename: Juliette
authors.initials: J
authors.lastname: Savoret
authors.affiliation: Innate-Pharma, 13009 Marseille, France;
authors.forename: Ivan
authors.initials: I
authors.lastname: Perrot
authors.affiliation: Institut des Sciences Pharmaceutiques et Biologiques, Université Lyon 1, Université de Lyon, 69373 Lyon, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5286, Département Immunité, Virus et Microenvironnement, Centre de Recherche en Cancérologie de Lyon, 69373 Lyon, France; INSERM U1052, Centre Léon Bérard, 69373 Lyon, France;
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Doffin
authors.affiliation: K.G. Jebsen Center for Research on Influenza Vaccines, University of Oslo and Oslo University Hospital, 0027 Oslo, Norway;
authors.forename: Even
authors.initials: E
authors.lastname: Fossum
authors.affiliation: Institut Paoli-Calmettes, 13009 Marseille, France;
authors.forename: Didier
authors.initials: D
authors.lastname: Bechlian
authors.affiliation: Institut Paoli-Calmettes, 13009 Marseille, France;
authors.forename: Christian
authors.initials: C
authors.lastname: Chabannon
authors.affiliation: K.G. Jebsen Center for Research on Influenza Vaccines, University of Oslo and Oslo University Hospital, 0027 Oslo, Norway; Center for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway; and.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.affiliation: Innate-Pharma, 13009 Marseille, France;
authors.forename: Carine
authors.initials: C
authors.lastname: Asselin-Paturel
authors.affiliation: Sanofi, Cambridge, MA 02139;
authors.forename: Michael
authors.initials: M
authors.lastname: Shaw
authors.affiliation: Sanofi, Cambridge, MA 02139;
authors.forename: Timothy
authors.initials: T
authors.lastname: Soos
authors.affiliation: Institut des Sciences Pharmaceutiques et Biologiques, Université Lyon 1, Université de Lyon, 69373 Lyon, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5286, Département Immunité, Virus et Microenvironnement, Centre de Recherche en Cancérologie de Lyon, 69373 Lyon, France; INSERM U1052, Centre Léon Bérard, 69373 Lyon, France; LabEx DEVweCAN, 69373 Lyon, France;
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.affiliation: Institut des Sciences Pharmaceutiques et Biologiques, Université Lyon 1, Université de Lyon, 69373 Lyon, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 5286, Département Immunité, Virus et Microenvironnement, Centre de Recherche en Cancérologie de Lyon, 69373 Lyon, France; INSERM U1052, Centre Léon Bérard, 69373 Lyon, France; LabEx DEVweCAN, 69373 Lyon, France;
authors.forename: Jenny
authors.initials: J
authors.lastname: Valladeau-Guilemond
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, UNIV UM2, Aix-Marseille Université, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France; INSERM, Unité Mixte de Recherche 1104, 13288 Marseille, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille, France; LabEx DCBIOL, 13288 Marseille, France dalod@ciml.univ-mrs.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology; D018952:Antigens, CD34 / Q000276:immunology*; D001773:Blood Cells / Q000276:immunology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins; D006801:Humans; D007093:Imidazoles / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D010641:Phenotype; D011070:Poly I-C / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4
chemical_list: D000276:Adjuvants, Immunologic; D018952:Antigens, CD34; D007093:Imidazoles; D008070:Lipopolysaccharides; D043562:Receptors, G-Protein-Coupled; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; C091671:XCR1 protein, human; D049452:Green Fluorescent Proteins; D011070:Poly I-C; C402365:resiquimod