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Brain endothelial tricellular junctions as novel sites for T cell diapedesis across the blood–brain barrier.
- Source :
-
Journal of Cell Science . Apr2021, Vol. 134 Issue 8, p1-19. 19p. - Publication Year :
- 2021
-
Abstract
- 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 proteinbased targeting of their interactions in pMBMECmonolayers 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219533
- Volume :
- 134
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Journal of Cell Science
- Publication Type :
- Academic Journal
- Accession number :
- 150879679
- Full Text :
- https://doi.org/10.1242/jcs.253880