title: Homeostatic NF-κB Signaling in Steady-State Migratory Dendritic Cells Regulates Immune Homeostasis and Tolerance.
abstract: Migratory non-lymphoid tissue dendritic cells (NLT-DCs) transport antigens to lymph nodes (LNs) and are required for protective immune responses in the context of inflammation and to promote tolerance to self-antigens in steady-state. However, the molecular mechanisms that elicit steady-state NLT-DC maturation and migration are unknown. By comparing the transcriptome of NLT-DCs in the skin with their migratory counterparts in draining LNs, we have identified a novel NF-κB-regulated gene network specific to migratory DCs. We show that targeted deletion of IKKβ in DCs, a major activator of NF-κB, prevents NLT-DC accumulation in LNs and compromises regulatory T cell conversion in vivo. This was associated with impaired tolerance and autoimmunity. NF-κB is generally considered the prototypical pro-inflammatory transcription factor, but this study describes a role for NF-κB signaling in DCs for immune homeostasis and tolerance that could have implications in autoimmune diseases and immunity.
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors: Myriam
authors: M
authors: Baratin
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors: Chloe
authors: C
authors: Foray
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors: Olivier
authors: O
authors: Demaria
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors: Mohamed
authors: M
authors: Habbeddine
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors: Emeline
authors: E
authors: Pollet
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors: Julien
authors: J
authors: Maurizio
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors: Christophe
authors: C
authors: Verthuy
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors: Suzel
authors: S
authors: Davanture
authors: Osaka University, Osaka 565-0871, Japan.
authors: Hiroaki
authors: H
authors: Azukizawa
authors: IBR-MRC Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors: Adriana
authors: A
authors: Flores-Langarica
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France.
authors: Marc
authors: M
authors: Dalod
authors: Centre d'Immunologie de Marseille-Luminy (CIML), Aix-Marseille Université, UM2, 13288 Marseille, France; Institut National de la Santé et de la Recherche Médicale (INSERM), U1104, 13288 Marseille, France; Centre National de la Recherche Scientifique (CNRS), UMR7280, 13288 Marseille, France. Electronic address: lawrence@ciml.univ-mrs.fr.
authors: Toby
authors: T
authors: Lawrence
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology*; D051550:I-kappa B Kinase / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D046228:Microarray Analysis; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D012867:Skin / Q000166:cytology / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology
chemical_list: D001324:Autoantigens; D016328:NF-kappa B; D051550:I-kappa B Kinase