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

Castro Dias, Mariana; Odriozola Quesada, Adolfo; Soldati, Sasha; Bösch, Fabio; Gruber, Isabelle; Hildbrand, Tobias; Sönmez, Derya; Khire, Tejas; Witz, Guillaume; McGrath, James L.; Piontek, Jörg; Kondoh, Masuo; Deutsch, Urban; Zuber, Benoît; Engelhardt, Britta (2021). Brain endothelial tricellular junctions as novel sites for T cell diapedesis across the blood–brain barrier. Journal of cell science, 134(8) Company of Biologists Limited 10.1242/jcs.253880

jcs253880.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (13MB) | Preview

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.

Item Type:

Journal Article (Original Article)


09 Interdisciplinary Units > Microscopy Imaging Center (MIC)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
08 Faculty of Science > Department of Mathematics and Statistics > Institute of Mathematics

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Mota Castro Dias, Mariana, Odriozola Quesada, Adolfo, Soldati, Sasha Giulio Natale, Gruber, Isabelle Manuela, Witz, Guillaume Robert, Deutsch, Urban, Zuber, Benoît, Engelhardt, Britta


600 Technology > 610 Medicine & health
500 Science > 510 Mathematics




Company of Biologists Limited




Benoît Zuber

Date Deposited:

31 May 2021 10:20

Last Modified:

05 Dec 2022 15:51

Publisher DOI:


PubMed ID:





Actions (login required)

Edit item Edit item
Provide Feedback