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Brain Sci. 2018 Mar 22;8(4). pii: E50. doi: 10.3390/brainsci8040050.

Connexin 43 Controls the Astrocyte Immunoregulatory Phenotype.

Author information

1
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, U1050/75231 Paris CEDEX 05, France. anne-cecile.boulay@college-de-france.fr.
2
Paris Science Lettre Research University, 75005 Paris, France. anne-cecile.boulay@college-de-france.fr.
3
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, U1050/75231 Paris CEDEX 05, France. alice.gilbert@college-de-france.fr.
4
Paris Science Lettre Research University, 75005 Paris, France. alice.gilbert@college-de-france.fr.
5
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, U1050/75231 Paris CEDEX 05, France. vanessa.oliveira-moreira@college-de-france.fr.
6
Paris Science Lettre Research University, 75005 Paris, France. vanessa.oliveira-moreira@college-de-france.fr.
7
Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, Genomic Facility, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005 Paris, France. blugeon@biologie.ens.fr.
8
Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, Genomic Facility, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005 Paris, France. sandrine.perrin7@free.fr.
9
Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, Genomic Facility, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005 Paris, France. juliette.hamroune@inserm.fr.
10
Laboratoire de Physique Statistique-ENS CNRS UMR 8550, 75005 Paris, France. juliette.hamroune@inserm.fr.
11
PSL Research University, Université Paris Diderot Sorbonne Paris-Cité, Sorbonne Universités UPMC Univ Paris 06, CNRS, 75005 Paris, France. juliette.hamroune@inserm.fr.
12
High Throughput qPCR Core Facility, IBENS, 46 rue d'Ulm, 75005 Paris, France. juliette.hamroune@inserm.fr.
13
Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, Genomic Facility, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005 Paris, France. lecrom@biologie.ens.fr.
14
Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, Genomic Facility, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Université Paris, 75005 Paris, France. bertrand.ducos@lps.ens.fr.
15
Laboratoire de Physique Statistique-ENS CNRS UMR 8550, 75005 Paris, France. bertrand.ducos@lps.ens.fr.
16
PSL Research University, Université Paris Diderot Sorbonne Paris-Cité, Sorbonne Universités UPMC Univ Paris 06, CNRS, 75005 Paris, France. bertrand.ducos@lps.ens.fr.
17
High Throughput qPCR Core Facility, IBENS, 46 rue d'Ulm, 75005 Paris, France. bertrand.ducos@lps.ens.fr.
18
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, U1050/75231 Paris CEDEX 05, France. martine.cohen-salmon@college-de-france.fr.
19
Paris Science Lettre Research University, 75005 Paris, France. martine.cohen-salmon@college-de-france.fr.

Abstract

Astrocytes are the most abundant glial cells of the central nervous system and have recently been recognized as crucial in the regulation of brain immunity. In most neuropathological conditions, astrocytes are prone to a radical phenotypical change called reactivity, which plays a key role in astrocyte contribution to neuroinflammation. However, how astrocytes regulate brain immunity in healthy conditions is an understudied question. One of the astroglial molecule involved in these regulations might be Connexin 43 (Cx43), a gap junction protein highly enriched in astrocyte perivascular endfeet-terminated processes forming the glia limitans. Indeed, Cx43 deletion in astrocytes (Cx43KO) promotes a continuous immune recruitment and an autoimmune response against an astrocyte protein, without inducing any brain lesion. To investigate the molecular basis of this unique immune response, we characterized the polysomal transcriptome of hippocampal astrocytes deleted for Cx43. Our results demonstrate that, in the absence of Cx43, astrocytes adopt an atypical reactive status with no change in most canonical astrogliosis markers, but with an upregulation of molecules promoting immune recruitment, complement activation as well as anti-inflammatory processes. Intriguingly, while several of these upregulated transcriptional events suggested an activation of the γ-interferon pathway, no increase in this cytokine or activation of related signaling pathways were found in Cx43KO. Finally, deletion of astroglial Cx43 was associated with the upregulation of several angiogenic factors, consistent with an increase in microvascular density in Cx43KO brains. Collectively, these results strongly suggest that Cx43 controls immunoregulatory and angiogenic properties of astrocytes.

KEYWORDS:

astrocyte; connexin 43; immunity; inflammation; ribosomal-bound transcriptome

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