Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells

Abstract The choroid plexus (CP) is strategically located between the peripheral blood and the cerebrospinal fluid, and is involved in the regulation of central nervous system (CNS) homeostasis. In multiple sclerosis (MS), demyelination and inflammation occur in the CNS. While experimental animal mo...

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Main Authors: Sabela Rodríguez-Lorenzo, Julia Konings, Susanne van der Pol, Alwin Kamermans, Sandra Amor, Jack van Horssen, Maarten E. Witte, Gijs Kooij, Helga E. de Vries
Format: Article
Language:English
Published: BMC 2020-02-01
Series:Acta Neuropathologica Communications
Subjects:
Online Access:https://doi.org/10.1186/s40478-020-0885-1
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author Sabela Rodríguez-Lorenzo
Julia Konings
Susanne van der Pol
Alwin Kamermans
Sandra Amor
Jack van Horssen
Maarten E. Witte
Gijs Kooij
Helga E. de Vries
author_facet Sabela Rodríguez-Lorenzo
Julia Konings
Susanne van der Pol
Alwin Kamermans
Sandra Amor
Jack van Horssen
Maarten E. Witte
Gijs Kooij
Helga E. de Vries
author_sort Sabela Rodríguez-Lorenzo
collection DOAJ
description Abstract The choroid plexus (CP) is strategically located between the peripheral blood and the cerebrospinal fluid, and is involved in the regulation of central nervous system (CNS) homeostasis. In multiple sclerosis (MS), demyelination and inflammation occur in the CNS. While experimental animal models of MS pointed to the CP as a key route for immune cell invasion of the CNS, little is known about the distribution of immune cells in the human CP during progressive phases of MS. Here, we use immunohistochemistry and confocal microscopy to explore the main immune cell populations in the CP of progressive MS patients and non-neuroinflammatory controls, in terms of abundance and location within the distinct CP compartments. We show for the first time that the CP stromal density of granulocytes and CD8+ T cells is higher in progressive MS patients compared to controls. In line with previous studies, the CP of both controls and progressive MS patients contains relatively high numbers of macrophages and dendritic cells. Moreover, we found virtually no B cells or plasma cells in the CP. MHCII+ antigen-presenting cells were often found in close proximity to T cells, suggesting constitutive CNS immune monitoring functions of the CP. Together, our data highlights the role of the CP in immune homeostasis and indicates the occurrence of mild inflammatory processes in the CP of progressive MS patients. However, our findings suggest that the CP is only marginally involved in immune cell migration into the CNS in chronic MS.
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spelling doaj.art-8c7ddcfe2bec45a086daa724750ab49d2022-12-21T21:56:17ZengBMCActa Neuropathologica Communications2051-59602020-02-018111310.1186/s40478-020-0885-1Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cellsSabela Rodríguez-Lorenzo0Julia Konings1Susanne van der Pol2Alwin Kamermans3Sandra Amor4Jack van Horssen5Maarten E. Witte6Gijs Kooij7Helga E. de Vries8Department of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, AmsterdamUMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, AmsterdamUMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, AmsterdamUMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, AmsterdamUMC, Vrije Universiteit AmsterdamDepartment of Pathology, MS center Amsterdam, Amsterdam UMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, AmsterdamUMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, AmsterdamUMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, AmsterdamUMC, Vrije Universiteit AmsterdamDepartment of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, AmsterdamUMC, Vrije Universiteit AmsterdamAbstract The choroid plexus (CP) is strategically located between the peripheral blood and the cerebrospinal fluid, and is involved in the regulation of central nervous system (CNS) homeostasis. In multiple sclerosis (MS), demyelination and inflammation occur in the CNS. While experimental animal models of MS pointed to the CP as a key route for immune cell invasion of the CNS, little is known about the distribution of immune cells in the human CP during progressive phases of MS. Here, we use immunohistochemistry and confocal microscopy to explore the main immune cell populations in the CP of progressive MS patients and non-neuroinflammatory controls, in terms of abundance and location within the distinct CP compartments. We show for the first time that the CP stromal density of granulocytes and CD8+ T cells is higher in progressive MS patients compared to controls. In line with previous studies, the CP of both controls and progressive MS patients contains relatively high numbers of macrophages and dendritic cells. Moreover, we found virtually no B cells or plasma cells in the CP. MHCII+ antigen-presenting cells were often found in close proximity to T cells, suggesting constitutive CNS immune monitoring functions of the CP. Together, our data highlights the role of the CP in immune homeostasis and indicates the occurrence of mild inflammatory processes in the CP of progressive MS patients. However, our findings suggest that the CP is only marginally involved in immune cell migration into the CNS in chronic MS.https://doi.org/10.1186/s40478-020-0885-1Choroid plexusProgressive MSImmune cellsT cellsGranulocytesBlood-CSF barrier
spellingShingle Sabela Rodríguez-Lorenzo
Julia Konings
Susanne van der Pol
Alwin Kamermans
Sandra Amor
Jack van Horssen
Maarten E. Witte
Gijs Kooij
Helga E. de Vries
Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells
Acta Neuropathologica Communications
Choroid plexus
Progressive MS
Immune cells
T cells
Granulocytes
Blood-CSF barrier
title Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells
title_full Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells
title_fullStr Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells
title_full_unstemmed Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells
title_short Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells
title_sort inflammation of the choroid plexus in progressive multiple sclerosis accumulation of granulocytes and t cells
topic Choroid plexus
Progressive MS
Immune cells
T cells
Granulocytes
Blood-CSF barrier
url https://doi.org/10.1186/s40478-020-0885-1
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