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Human CD4(+) T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro
BACKGROUND: The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996191/ https://www.ncbi.nlm.nih.gov/pubmed/32008573 http://dx.doi.org/10.1186/s12987-019-0165-2 |
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author | Nishihara, Hideaki Soldati, Sasha Mossu, Adrien Rosito, Maria Rudolph, Henriette Muller, William A. Latorre, Daniela Sallusto, Federica Sospedra, Mireia Martin, Roland Ishikawa, Hiroshi Tenenbaum, Tobias Schroten, Horst Gosselet, Fabien Engelhardt, Britta |
author_facet | Nishihara, Hideaki Soldati, Sasha Mossu, Adrien Rosito, Maria Rudolph, Henriette Muller, William A. Latorre, Daniela Sallusto, Federica Sospedra, Mireia Martin, Roland Ishikawa, Hiroshi Tenenbaum, Tobias Schroten, Horst Gosselet, Fabien Engelhardt, Britta |
author_sort | Nishihara, Hideaki |
collection | PubMed |
description | BACKGROUND: The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood–brain barrier (BBB) or the epithelial blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP). OBJECTIVE: Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4(+) T-cell subsets across the BBB versus the BCSFB. METHODS: Human in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4(+) T helper cell subsets (Th1, Th1*, Th2, Th17) across the BBB and BCSFB under inflammatory and non-inflammatory conditions in vitro. RESULTS: While under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10- to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barrier-crossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration. CONCLUSIONS: Our observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB. |
format | Online Article Text |
id | pubmed-6996191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69961912020-02-05 Human CD4(+) T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro Nishihara, Hideaki Soldati, Sasha Mossu, Adrien Rosito, Maria Rudolph, Henriette Muller, William A. Latorre, Daniela Sallusto, Federica Sospedra, Mireia Martin, Roland Ishikawa, Hiroshi Tenenbaum, Tobias Schroten, Horst Gosselet, Fabien Engelhardt, Britta Fluids Barriers CNS Research BACKGROUND: The brain barriers establish compartments in the central nervous system (CNS) that significantly differ in their communication with the peripheral immune system. In this function they strictly control T-cell entry into the CNS. T cells can reach the CNS by either crossing the endothelial blood–brain barrier (BBB) or the epithelial blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP). OBJECTIVE: Analysis of the cellular and molecular mechanisms involved in the migration of different human CD4(+) T-cell subsets across the BBB versus the BCSFB. METHODS: Human in vitro models of the BBB and BCSFB were employed to study the migration of circulating and CNS-entry experienced CD4(+) T helper cell subsets (Th1, Th1*, Th2, Th17) across the BBB and BCSFB under inflammatory and non-inflammatory conditions in vitro. RESULTS: While under non-inflammatory conditions Th1* and Th1 cells preferentially crossed the BBB, under inflammatory conditions the migration rate of all Th subsets across the BBB was comparable. The migration of all Th subsets across the BCSFB from the same donor was 10- to 20-fold lower when compared to their migration across the BBB. Interestingly, Th17 cells preferentially crossed the BCSFB under both, non-inflamed and inflamed conditions. Barrier-crossing experienced Th cells sorted from CSF of MS patients showed migratory characteristics indistinguishable from those of circulating Th cells of healthy donors. All Th cell subsets could additionally cross the BCSFB from the CSF to ChP stroma side. T-cell migration across the BCSFB involved epithelial ICAM-1 irrespective of the direction of migration. CONCLUSIONS: Our observations underscore that different Th subsets may use different anatomical routes to enter the CNS during immune surveillance versus neuroinflammation with the BCSFB establishing a tighter barrier for T-cell entry into the CNS compared to the BBB. In addition, CNS-entry experienced Th cell subsets isolated from the CSF of MS patients do not show an increased ability to cross the brain barriers when compared to circulating Th cell subsets from healthy donors underscoring the active role of the brain barriers in controlling T-cell entry into the CNS. Also we identify ICAM-1 to mediate T cell migration across the BCSFB. BioMed Central 2020-02-03 /pmc/articles/PMC6996191/ /pubmed/32008573 http://dx.doi.org/10.1186/s12987-019-0165-2 Text en © The Author(s) 2020 Open AccessThis 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. |
spellingShingle | Research Nishihara, Hideaki Soldati, Sasha Mossu, Adrien Rosito, Maria Rudolph, Henriette Muller, William A. Latorre, Daniela Sallusto, Federica Sospedra, Mireia Martin, Roland Ishikawa, Hiroshi Tenenbaum, Tobias Schroten, Horst Gosselet, Fabien Engelhardt, Britta Human CD4(+) T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro |
title | Human CD4(+) T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro |
title_full | Human CD4(+) T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro |
title_fullStr | Human CD4(+) T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro |
title_full_unstemmed | Human CD4(+) T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro |
title_short | Human CD4(+) T cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro |
title_sort | human cd4(+) t cell subsets differ in their abilities to cross endothelial and epithelial brain barriers in vitro |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996191/ https://www.ncbi.nlm.nih.gov/pubmed/32008573 http://dx.doi.org/10.1186/s12987-019-0165-2 |
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