Journal of Neuroscience 2015-03-11

Immune quiescence of the brain is set by astroglial connexin 43.

Anne-Cécile Boulay, Aurélien Mazeraud, Salvatore Cisternino, Bruno Saubaméa, Phillipe Mailly, Laurent Jourdren, Corinne Blugeon, Virginie Mignon, Maria Smirnova, Alessia Cavallo, Pascal Ezan, Patrick Avé, Florent Dingli, Damarys Loew, Paulo Vieira, Fabrice Chrétien, Martine Cohen-Salmon

Index: J. Neurosci. 35(10) , 4427-39, (2015)

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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. Copyright © 2015 the authors 0270-6474/15/354427-13$15.00/0.