title: Immune quiescence of the brain is set by astroglial connexin 43.
abstract: In the normal brain, immune cell trafficking and immune responses are strictly controlled and limited. This unique homeostatic equilibrium, also called brain immune quiescence, is crucial to maintaining proper brain functions and is altered in various pathological processes, from chronic immunopathological disorders to cognitive and psychiatric impairments. To date, the precise nature of factors regulating the brain/immune system interrelationship is poorly understood. In the present study, we demonstrate that one of these regulating factors is Connexin 43 (Cx43), a gap junction protein highly expressed by astrocytes at the blood-brain barrier (BBB) interface. We show that, by setting the activated state of cerebral endothelium, astroglial Cx43 controls immune recruitment as well as antigen presentation mechanisms in the mouse brain. Consequently, in the absence of astroglial Cx43, recruited immune cells elaborate a specific humoral autoimmune response against the von Willebrand factor A domain-containing protein 5a, an extracellular matrix protein of the brain. Altogether, our results demonstrate that Cx43 is a new astroglial factor promoting the immune quiescence of the brain.
authors.affiliation: College of France, Center for Interdisciplinary Research in Biology/National Center of Scientific Research (CNRS), Coeducational Research Unit (UMR) 7241, National Institute of Health and Medical Research (INSERM), U1050/Neuroglial Interactions in Cerebral Physiopathology, F-75231 Paris, France, University Pierre and Marie Curie, F-75005 Paris, France, MemoLife Laboratory of Excellence and Paris Science Lettre Research University, F-75005 Paris, France.
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Boulay
authors.affiliation: Human Histopathology and Animal Models and Paris Descartes University-Sorbonne Paris Cité and Neuropathology Service, Sainte-Anne Hospital Center, F-75014 Paris, France.
authors.forename: Aurélien
authors.identifier: http://orcid.org/0000-0001-8473-7779
authors.initials: A
authors.lastname: Mazeraud
authors.affiliation: Faculté de Pharmacie, UMR in Health 1144, F-75006 Paris, France, Psychotropic Response Variability, INSERM, U1144, Paris, F-75006, France, Paris Diderot University, Coeducational Research Unit in Health 1144, F-75013 Paris, France.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cisternino
authors.affiliation: Faculté de Pharmacie, UMR in Health 1144, F-75006 Paris, France, Psychotropic Response Variability, INSERM, U1144, Paris, F-75006, France, Paris Diderot University, Coeducational Research Unit in Health 1144, F-75013 Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Saubaméa
authors.affiliation: College of France, Center for Interdisciplinary Research in Biology/National Center of Scientific Research (CNRS), Coeducational Research Unit (UMR) 7241, National Institute of Health and Medical Research (INSERM), U1050/Neuroglial Interactions in Cerebral Physiopathology, F-75231 Paris, France, University Pierre and Marie Curie, F-75005 Paris, France, MemoLife Laboratory of Excellence and Paris Science Lettre Research University, F-75005 Paris, France.
authors.forename: Phillipe
authors.initials: P
authors.lastname: Mailly
authors.affiliation: Ecole Normale Supérieure, Institute of Biology, Genomic Platform, F-75005 Paris, France, INSERM, U1024, F-75005 Paris, France, CNRS, UMR 8197, Paris, F-75005 France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Jourdren
authors.affiliation: Ecole Normale Supérieure, Institute of Biology, Genomic Platform, F-75005 Paris, France, INSERM, U1024, F-75005 Paris, France, CNRS, UMR 8197, Paris, F-75005 France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Blugeon
authors.affiliation: Faculté de Pharmacie, UMR in Health 1144, F-75006 Paris, France, Psychotropic Response Variability, INSERM, U1144, Paris, F-75006, France, Paris Diderot University, Coeducational Research Unit in Health 1144, F-75013 Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Mignon
authors.affiliation: Faculté de Pharmacie, UMR in Health 1144, F-75006 Paris, France, Psychotropic Response Variability, INSERM, U1144, Paris, F-75006, France, Paris Diderot University, Coeducational Research Unit in Health 1144, F-75013 Paris, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Smirnova
authors.affiliation: College of France, Center for Interdisciplinary Research in Biology/National Center of Scientific Research (CNRS), Coeducational Research Unit (UMR) 7241, National Institute of Health and Medical Research (INSERM), U1050/Neuroglial Interactions in Cerebral Physiopathology, F-75231 Paris, France, University Pierre and Marie Curie, F-75005 Paris, France, MemoLife Laboratory of Excellence and Paris Science Lettre Research University, F-75005 Paris, France.
authors.forename: Alessia
authors.initials: A
authors.lastname: Cavallo
authors.affiliation: College of France, Center for Interdisciplinary Research in Biology/National Center of Scientific Research (CNRS), Coeducational Research Unit (UMR) 7241, National Institute of Health and Medical Research (INSERM), U1050/Neuroglial Interactions in Cerebral Physiopathology, F-75231 Paris, France, University Pierre and Marie Curie, F-75005 Paris, France, MemoLife Laboratory of Excellence and Paris Science Lettre Research University, F-75005 Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Ezan
authors.affiliation: Human Histopathology and Animal Models and Paris Descartes University-Sorbonne Paris Cité and Neuropathology Service, Sainte-Anne Hospital Center, F-75014 Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Avé
authors.affiliation: Curie Institute Research Center, Protein Mass Spectrometry Laboratory, F-75248 Paris, France, and.
authors.forename: Florent
authors.identifier: http://orcid.org/0000-0002-7715-2446
authors.initials: F
authors.lastname: Dingli
authors.affiliation: Curie Institute Research Center, Protein Mass Spectrometry Laboratory, F-75248 Paris, France, and.
authors.forename: Damarys
authors.initials: D
authors.lastname: Loew
authors.affiliation: Lymphopoiesis Unit, Pasteur Institute, F-75015 Paris, France, INSERM, U668, F-75015 Paris, France.
authors.forename: Paulo
authors.initials: P
authors.lastname: Vieira
authors.affiliation: Human Histopathology and Animal Models and Paris Descartes University-Sorbonne Paris Cité and Neuropathology Service, Sainte-Anne Hospital Center, F-75014 Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chrétien
authors.affiliation: College of France, Center for Interdisciplinary Research in Biology/National Center of Scientific Research (CNRS), Coeducational Research Unit (UMR) 7241, National Institute of Health and Medical Research (INSERM), U1050/Neuroglial Interactions in Cerebral Physiopathology, F-75231 Paris, France, University Pierre and Marie Curie, F-75005 Paris, France, MemoLife Laboratory of Excellence and Paris Science Lettre Research University, F-75005 Paris, France, martine.cohen-salmon@college-de-france.fr.
authors.forename: Martine
authors.identifier: http://orcid.org/0000-0002-5312-8476
authors.initials: M
authors.lastname: Cohen-Salmon
mesh_terms: D000367:Age Factors; D000418:Albumins / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000166:cytology* / Q000276:immunology*; D017252:CD3 Complex / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein; D056724:Immunity, Humoral / Q000235:genetics / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D013395:Sucrose / Q000493:pharmacokinetics
chemical_list: C491049:Aif1 protein, mouse; D000418:Albumins; D017252:CD3 Complex; D002135:Calcium-Binding Proteins; D002247:Carbon Isotopes; D018031:Connexin 43; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009418:S100 Proteins; C528900:glial fibrillary astrocytic protein, mouse; D013395:Sucrose
keywords: astrocyte; autoimmunity; blood-brain barrier; connexin; immune quiescence