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MCAM(+) brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4(+) T lymphocytes
The trafficking of autoreactive leucocytes across the blood–brain barrier endothelium is a hallmark of multiple sclerosis pathogenesis. Although the blood–brain barrier endothelium represents one of the main CNS borders to interact with the infiltrating leucocytes, its exact contribution to neuroinf...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10115172/ https://www.ncbi.nlm.nih.gov/pubmed/36319587 http://dx.doi.org/10.1093/brain/awac389 |
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author | Charabati, Marc Zandee, Stephanie Fournier, Antoine P Tastet, Olivier Thai, Karine Zaminpeyma, Roxaneh Lécuyer, Marc-André Bourbonnière, Lyne Larouche, Sandra Klement, Wendy Grasmuck, Camille Tea, Fiona Zierfuss, Bettina Filali-Mouhim, Ali Moumdjian, Robert Bouthillier, Alain Cayrol, Romain Peelen, Evelyn Arbour, Nathalie Larochelle, Catherine Prat, Alexandre |
author_facet | Charabati, Marc Zandee, Stephanie Fournier, Antoine P Tastet, Olivier Thai, Karine Zaminpeyma, Roxaneh Lécuyer, Marc-André Bourbonnière, Lyne Larouche, Sandra Klement, Wendy Grasmuck, Camille Tea, Fiona Zierfuss, Bettina Filali-Mouhim, Ali Moumdjian, Robert Bouthillier, Alain Cayrol, Romain Peelen, Evelyn Arbour, Nathalie Larochelle, Catherine Prat, Alexandre |
author_sort | Charabati, Marc |
collection | PubMed |
description | The trafficking of autoreactive leucocytes across the blood–brain barrier endothelium is a hallmark of multiple sclerosis pathogenesis. Although the blood–brain barrier endothelium represents one of the main CNS borders to interact with the infiltrating leucocytes, its exact contribution to neuroinflammation remains understudied. Here, we show that Mcam identifies inflammatory brain endothelial cells with pro-migratory transcriptomic signature during experimental autoimmune encephalomyelitis. In addition, MCAM was preferentially upregulated on blood–brain barrier endothelial cells in multiple sclerosis lesions in situ and at experimental autoimmune encephalomyelitis disease onset by molecular MRI. In vitro and in vivo, we demonstrate that MCAM on blood–brain barrier endothelial cells contributes to experimental autoimmune encephalomyelitis development by promoting the cellular trafficking of T(H)1 and T(H)17 lymphocytes across the blood–brain barrier. Last, we showcase ST14 as an immune ligand to brain endothelial MCAM, enriched on CD4(+) T lymphocytes that cross the blood–brain barrier in vitro, in vivo and in multiple sclerosis lesions as detected by flow cytometry on rapid autopsy derived brain tissue from multiple sclerosis patients. Collectively, our findings reveal that MCAM is at the centre of a pathological pathway used by brain endothelial cells to recruit pathogenic CD4(+) T lymphocyte from circulation early during neuroinflammation. The therapeutic targeting of this mechanism is a promising avenue to treat multiple sclerosis. |
format | Online Article Text |
id | pubmed-10115172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-101151722023-04-20 MCAM(+) brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4(+) T lymphocytes Charabati, Marc Zandee, Stephanie Fournier, Antoine P Tastet, Olivier Thai, Karine Zaminpeyma, Roxaneh Lécuyer, Marc-André Bourbonnière, Lyne Larouche, Sandra Klement, Wendy Grasmuck, Camille Tea, Fiona Zierfuss, Bettina Filali-Mouhim, Ali Moumdjian, Robert Bouthillier, Alain Cayrol, Romain Peelen, Evelyn Arbour, Nathalie Larochelle, Catherine Prat, Alexandre Brain Original Article The trafficking of autoreactive leucocytes across the blood–brain barrier endothelium is a hallmark of multiple sclerosis pathogenesis. Although the blood–brain barrier endothelium represents one of the main CNS borders to interact with the infiltrating leucocytes, its exact contribution to neuroinflammation remains understudied. Here, we show that Mcam identifies inflammatory brain endothelial cells with pro-migratory transcriptomic signature during experimental autoimmune encephalomyelitis. In addition, MCAM was preferentially upregulated on blood–brain barrier endothelial cells in multiple sclerosis lesions in situ and at experimental autoimmune encephalomyelitis disease onset by molecular MRI. In vitro and in vivo, we demonstrate that MCAM on blood–brain barrier endothelial cells contributes to experimental autoimmune encephalomyelitis development by promoting the cellular trafficking of T(H)1 and T(H)17 lymphocytes across the blood–brain barrier. Last, we showcase ST14 as an immune ligand to brain endothelial MCAM, enriched on CD4(+) T lymphocytes that cross the blood–brain barrier in vitro, in vivo and in multiple sclerosis lesions as detected by flow cytometry on rapid autopsy derived brain tissue from multiple sclerosis patients. Collectively, our findings reveal that MCAM is at the centre of a pathological pathway used by brain endothelial cells to recruit pathogenic CD4(+) T lymphocyte from circulation early during neuroinflammation. The therapeutic targeting of this mechanism is a promising avenue to treat multiple sclerosis. Oxford University Press 2022-11-02 /pmc/articles/PMC10115172/ /pubmed/36319587 http://dx.doi.org/10.1093/brain/awac389 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Article Charabati, Marc Zandee, Stephanie Fournier, Antoine P Tastet, Olivier Thai, Karine Zaminpeyma, Roxaneh Lécuyer, Marc-André Bourbonnière, Lyne Larouche, Sandra Klement, Wendy Grasmuck, Camille Tea, Fiona Zierfuss, Bettina Filali-Mouhim, Ali Moumdjian, Robert Bouthillier, Alain Cayrol, Romain Peelen, Evelyn Arbour, Nathalie Larochelle, Catherine Prat, Alexandre MCAM(+) brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4(+) T lymphocytes |
title | MCAM(+) brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4(+) T lymphocytes |
title_full | MCAM(+) brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4(+) T lymphocytes |
title_fullStr | MCAM(+) brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4(+) T lymphocytes |
title_full_unstemmed | MCAM(+) brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4(+) T lymphocytes |
title_short | MCAM(+) brain endothelial cells contribute to neuroinflammation by recruiting pathogenic CD4(+) T lymphocytes |
title_sort | mcam(+) brain endothelial cells contribute to neuroinflammation by recruiting pathogenic cd4(+) t lymphocytes |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10115172/ https://www.ncbi.nlm.nih.gov/pubmed/36319587 http://dx.doi.org/10.1093/brain/awac389 |
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