Brain endothelial tricellular junctions as novel sites for T cell diapedesis across the blood-brain barrier.

Animals Biological Transport Blood-Brain Barrier Endothelial Cells Mice T-Lymphocytes Tight Junctions Transendothelial and Transepithelial Migration
Blood–brain barrier Diapedesis SBF-SEM T cells Tricellular junctions

Journal

Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457

Informations de publication

Date de publication:
15 04 2021
Historique:
received: 03 09 2020
accepted: 12 03 2021
entrez: 29 4 2021
pubmed: 30 4 2021
medline: 13 7 2021
Statut: ppublish

Résumé

The migration of activated T cells across the blood-brain barrier (BBB) is a critical step in central nervous system (CNS) immune surveillance and inflammation. Whereas T cell diapedesis across the intact BBB seems to occur preferentially through the BBB cellular junctions, impaired BBB integrity during neuroinflammation is accompanied by increased transcellular T cell diapedesis. The underlying mechanisms directing T cells to paracellular versus transcellular sites of diapedesis across the BBB remain to be explored. By combining in vitro live-cell imaging of T cell migration across primary mouse brain microvascular endothelial cells (pMBMECs) under physiological flow with serial block-face scanning electron microscopy (SBF-SEM), we have identified BBB tricellular junctions as novel sites for T cell diapedesis across the BBB. Downregulated expression of tricellular junctional proteins or protein-based targeting of their interactions in pMBMEC monolayers correlated with enhanced transcellular T cell diapedesis, and abluminal presence of chemokines increased T cell diapedesis through tricellular junctions. Our observations assign an entirely novel role to BBB tricellular junctions in regulating T cell entry into the CNS. This article has an associated First Person interview with the first author of the paper.

Identifiants

DOI: 10.1242/jcs.253880 PMID: 33912914 PMC: PMC8121105
pubmed: 33912914
pii: 237782
doi: 10.1242/jcs.253880
pmc: PMC8121105
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2021. Published by The Company of Biologists Ltd.

Déclaration de conflit d'intérêts

Competing interests The authors declare no competing or financial interests.

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Auteurs

Mariana Castro Dias (M)

Theodor Kocher Institute, University of Bern, Bern, Switzerland.

Adolfo Odriozola Quesada (A)

Institute of Anatomy, University of Bern, Bern CH-3012, Switzerland.

Sasha Soldati (S)

Theodor Kocher Institute, University of Bern, Bern, Switzerland.

Fabio Bösch (F)

Theodor Kocher Institute, University of Bern, Bern, Switzerland.

Isabelle Gruber (I)

Theodor Kocher Institute, University of Bern, Bern, Switzerland.

Tobias Hildbrand (T)

Theodor Kocher Institute, University of Bern, Bern, Switzerland.

Derya Sönmez (D)

Theodor Kocher Institute, University of Bern, Bern, Switzerland.

Tejas Khire (T)

Department of Biomedical Engineering, University of Rochester, Rochester, NY 270168, USA.

Guillaume Witz (G)

Microscopy Imaging Center (MIC), University of Bern, Bern CH-3012, Switzerland.
Science IT Support (ScITS), Mathematical Institute, University of Bern, Bern CH-3012, Switzerland.

James L McGrath (JL)

Department of Biomedical Engineering, University of Rochester, Rochester, NY 270168, USA.

Jörg Piontek (J)

Institute of Clinical Physiology, Charité - Universitätsmedizin Berlin, Berlin 10117, Germany.

Masuo Kondoh (M)

Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.

Urban Deutsch (U)

Theodor Kocher Institute, University of Bern, Bern, Switzerland.

Benoît Zuber (B)

Institute of Anatomy, University of Bern, Bern CH-3012, Switzerland.

Britta Engelhardt (B)

Theodor Kocher Institute, University of Bern, Bern, Switzerland.

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Classifications MeSH

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Recherchemedicale.com › Système nerveux › Système nerveux central › Encéphale › Barrière hémato-encéphalique › Brain endothelial tricellular junctions as...
Recherchemedicale.com › Cellules › Cellules épithéliales › Cellules endothéliales › Brain endothelial tricellular junctions as...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Brain endothelial tricellular junctions as...
Recherchemedicale.com › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Brain endothelial tricellular junctions as...
Recherchemedicale.com › Cellules › Structures cellulaires › Membrane cellulaire › Structures de la membrane cellulaire › Jonctions intercellulaires › Jonctions serrées › Brain endothelial tricellular junctions as...
Recherchemedicale.com › Phénomènes physiologiques › Mouvement cellulaire › Migration transendothéliale et transépithéliale › Brain endothelial tricellular junctions as...