T-Cell Migration Across the Blood–Brain Barrier in CNS Inflammatory Diseases

2016 ◽  
Vol 46 (9) ◽  
pp. 2187-2203 ◽  
Author(s):  
Henriette Rudolph ◽  
Armelle Klopstein ◽  
Isabelle Gruber ◽  
Claudia Blatti ◽  
Ruth Lyck ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Linan Liu ◽  
Mark A. Eckert ◽  
Hamidreza Riazifar ◽  
Dong-Ku Kang ◽  
Dritan Agalliu ◽  
...  

Systemically infused mesenchymal stem cells (MSCs) are emerging therapeutics for treating stroke, acute injuries, and inflammatory diseases of the central nervous system (CNS), as well as brain tumors due to their regenerative capacity and ability to secrete trophic, immune modulatory, or other engineered therapeutic factors. It is hypothesized that transplanted MSCs home to and engraft at ischemic and injured sites in the brain in order to exert their therapeutic effects. However, whether MSCs possess the ability to migrate across the blood-brain barrier (BBB) that separates the blood from the brain remains unresolved. This review analyzes recent advances in this area in an attempt to elucidate whether systemically infused MSCs are able to actively transmigrate across the CNS endothelium, particularly under conditions of injury or stroke. Understanding the fate of transplanted MSCs and their CNS trafficking mechanisms will facilitate the development of more effective stem-cell-based therapeutics and drug delivery systems to treat neurological diseases and brain tumors.


2021 ◽  
Vol 134 (8) ◽  
Author(s):  
Mariana Castro Dias ◽  
Adolfo Odriozola Quesada ◽  
Sasha Soldati ◽  
Fabio Bösch ◽  
Isabelle Gruber ◽  
...  

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 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.


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