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J Neurosci. 2015 Mar 11;35(10):4427-39. doi: 10.1523/JNEUROSCI.2575-14.2015.

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

Author information

1
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.
2
Human Histopathology and Animal Models and Paris Descartes University-Sorbonne Paris Cité and Neuropathology Service, Sainte-Anne Hospital Center, F-75014 Paris, France.
3
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.
4
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.
5
Curie Institute Research Center, Protein Mass Spectrometry Laboratory, F-75248 Paris, France, and.
6
Lymphopoiesis Unit, Pasteur Institute, F-75015 Paris, France, INSERM, U668, F-75015 Paris, France.
7
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.

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.

KEYWORDS:

astrocyte; autoimmunity; blood-brain barrier; connexin; immune quiescence

PMID:
25762685
DOI:
10.1523/JNEUROSCI.2575-14.2015
[Indexed for MEDLINE]
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