title: Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery.
abstract: Dendritic cells (DCs) are instrumental in the initiation of T cell responses, but how thymic and peripheral tolerogenic DCs differ globally from Toll-like receptor (TLR)-induced immunogenic DCs remains unclear. Here, we show that thymic XCR1(+) DCs undergo a high rate of maturation, accompanied by profound gene-expression changes that are essential for central tolerance and also happen in germ-free mice. Those changes largely overlap those occurring during tolerogenic and, more unexpectedly, TLR-induced maturation of peripheral XCR1(+) DCs, arguing against the commonly held view that tolerogenic DCs undergo incomplete maturation. Interferon-stimulated gene (ISG) expression was among the few discriminators of immunogenic and tolerogenic XCR1(+) DCs. Tolerogenic XCR1(+) thymic DCs were, however, unique in expressing ISGs known to restrain virus replication. Therefore, a broad functional convergence characterizes tolerogenic and immunogenic XCR1(+) DC maturation in the thymus and periphery, maximizing antigen presentation and signal delivery to developing and to conventional and regulatory mature T cells.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Ardouin
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France; Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Luche
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Rabie
authors.initials: R
authors.lastname: Chelbi
authors.affiliation: MI-mAbs, Aix Marseille Université, 13288 Marseille, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Carpentier
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Alaa
authors.initials: A
authors.lastname: Shawket
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Montanana Sanchis
authors.affiliation: Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Santa Maria
authors.affiliation: Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Grenot
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Alexandre
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Grégoire
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Anissa
authors.initials: A
authors.lastname: Fries
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Thien-Phong
authors.initials: TP
authors.lastname: Vu Manh
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Samira
authors.initials: S
authors.lastname: Tamoutounour
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Crozat
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Elena
authors.initials: E
authors.lastname: Tomasello
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Jorquera
authors.affiliation: Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Even
authors.initials: E
authors.lastname: Fossum
authors.affiliation: Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, 0424 Oslo, Norway.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.affiliation: Department of Dermatology, Osaka University, Osaka 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Azukizawa
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bajenoff
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Henri
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France. Electronic address: dalod@ciml.univ-mrs.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Dalod
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France; Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, 13288 Marseille, France. Electronic address: bernardm@ciml.univ-mrs.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002454:Cell Differentiation; D002478:Cells, Cultured; D061167:Central Tolerance; D003713:Dendritic Cells / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061166:Peripheral Tolerance; D019707:Receptors, Chemokine / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology; D059467:Transcriptome; D014779:Virus Replication
chemical_list: D050835:Interferon Regulatory Factors; D019707:Receptors, Chemokine; D051193:Toll-Like Receptors; C551408:XC chemokine receptor 1, mouse