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Title: | Cerebral microvascular endothelial cell-derived extracellular vesicles regulate blood - brain barrier function | Authors: | HOSSEINKHANI, Baharak DURAN, Gayel HOEKS, Cindy HERMANS, Doryssa SCHEPERS, Melissa BAETEN, Paulien POELMANS, Joren Coenen, Britt Bekar, Kuebra Pintelon, Isabel Timmermans , Jean-Pierre VANMIERLO, Tim MICHIELS, Luc HELLINGS, Niels BROUX, Bieke |
Issue Date: | 2023 | Publisher: | BMC | Source: | Fluids and Barriers of the CNS, 20 (1) (Art N° 95) | Abstract: | Autoreactive T lymphocytes crossing the blood-brain barrier (BBB) into the central nervous system (CNS) play a crucial role in the initiation of demyelination and neurodegeneration in multiple sclerosis (MS). Recently, extracellular vesicles (EV) secreted by BBB endothelial cells (BBB-EC) have emerged as a unique form of cell-to-cell communication that contributes to cerebrovascular dysfunction. However, the precise impact of different size-based subpopulations of BBB-EC-derived EV (BBB-EV) on the early stages of MS remains unclear. Therefore, our objective was to investigate the content and function of distinct BBB-EV subpopulations in regulating BBB integrity and their role in T cell transendothelial migration, both in vitro and in vivo. Our study reveals that BBB-ECs release two distinct size based EV populations, namely small EV (sEV; 30-150 nm) and large EV (lEV; 150-300 nm), with a significantly higher secretion of sEV during inflammation. Notably, the expression patterns of cytokines and adhesion markers differ significantly between these BBB-EV subsets, indicating specific functional differences in the regulation of T cell migration. Through in vitro experiments, we demonstrate that lEV, which predominantly reflect their cellular source, play a major role in BBB integrity loss and the enhanced migration of pro-inflammatory Th1 and Th17.1 cells. Conversely, sEV appear to protect BBB function by inducing an anti-inflammatory phenotype in BBB-EC. These findings align with our in vivo data, where the administration of sEV to mice with experimental autoimmune encephalomyelitis (EAE) results in lower disease severity compared to the administration of lEV, which exacerbates disease symptoms. In conclusion, our study highlights the distinct and opposing effects of BBB-EV subpopulations on the BBB, both in vitro and in vivo. These findings underscore the need for further investigation into the diagnostic and therapeutic potential of BBB-EV in the context of MS. | Notes: | Broux, B (corresponding author), Univ MS Ctr, Campus Diepenbeek, Diepenbeek, Belgium.; Broux, B (corresponding author), Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Neuroimmune Connect & Repair Lab, Diepenbeek, Belgium.; Broux, B (corresponding author), Univ Hasselt, Martelarenlaan 42, Hasselt, Belgium. bieke.broux@uhasselt.be |
Keywords: | Multiple sclerosis;Multiple sclerosis;BBB;BBB;EV;EV | Document URI: | http://hdl.handle.net/1942/42079 | ISSN: | 2045-8118 | e-ISSN: | 2045-8118 | DOI: | 10.1186/s12987-023-00504-6 | ISI #: | 001127500800001 | Rights: | The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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