title: Immunoregulation at the gliovascular unit in the healthy brain: A focus on Connexin 43.
abstract: In the brain, immune cell infiltration is normally kept at a very low level and a unique microenvironment strictly restricts immune reactions and inflammation. Even in such quiescent environment, a constant immune surveillance is at work allowing the brain to rapidly react to threats. To date, knowledge about the factors regulating the brain-immune system interrelationship in healthy conditions remains elusive. Interestingly, astrocytes, the most abundant glial cells in the brain, may participate in many aspects of this unique homeostasis, in particular due to their close interaction with the brain vascular system and expression of a specific molecular repertoire. Indeed, astrocytes maintain the blood-brain barrier (BBB) integrity, interact with immune cells, and participate in the regulation of intracerebral liquid movements. We recently showed that Connexin 43 (Cx43), a gap junction protein highly expressed by astrocytes at the BBB interface, is an immunoregulating factor. The absence of astroglial Cx43 leads to a transient endothelial activation, a continuous immune recruitment as well as the development of a specific humoral autoimmune response against the von Willebrand factor A domain-containing protein 5a, an extracellular matrix protein expressed by astrocytes. In this review, we propose to gather current knowledge on how astrocytes may influence the immune system in the healthy brain, focusing on their roles at the gliovascular interface. We will also consider pathological situations involving astrocyte-specific autoimmunities. Finally, we will discuss the specific role of astroglial Cx43 and the physiological consequences of immune regulations taking place on inflammation, cognition and behavior in the absence of Cx43.
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Centre National de la Recherche Scientifique CNRS, Unité Mixte de Recherche 7241, Institut National de la Santé et de la Recherche Médicale INSERM, U1050, Neuroglial Interactions in Cerebral Physiopathology, 75231 Paris Cedex 05, France; University Pierre et Marie Curie, ED, N°158, 75005 Paris, France; MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France.
authors.forename: Anne-Cécile
authors.initials: AC
authors.lastname: Boulay
authors.affiliation: Variabilité de réponse aux psychotropes, INSERM, U1144, Paris F-75006, France; Université Paris Descartes, Faculté de Pharmacie, UMR-S 1144, 75006 Paris, France; Université Paris Diderot, UMR-S 1144, 75013 Paris, France.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cisternino
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology (CIRB), Centre National de la Recherche Scientifique CNRS, Unité Mixte de Recherche 7241, Institut National de la Santé et de la Recherche Médicale INSERM, U1050, Neuroglial Interactions in Cerebral Physiopathology, 75231 Paris Cedex 05, France; University Pierre et Marie Curie, ED, N°158, 75005 Paris, France; MEMOLIFE Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France. Electronic address: martine.cohen-salmon@college-de-france.fr.
authors.forename: Martine
authors.initials: M
authors.lastname: Cohen-Salmon
mesh_terms: D001253:Astrocytes / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001812:Blood-Brain Barrier / Q000276:immunology*; D001921:Brain / Q000276:immunology*; D018031:Connexin 43 / Q000502:physiology*; D006801:Humans
chemical_list: D018031:Connexin 43
keywords: Astrocytes; Connexin 43; Gliovascular unit; Immune quiescence; Immune surveillance