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Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system

Ependymal cells make up the epithelial monolayer that lines the brain ventricles and the spinal cord central canal that are filled with cerebrospinal fluid. The ependyma has several functions, including regulating solute exchange between the cerebrospinal fluid and parenchyma, controlling microcircu...

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Autores principales: Bigotte, Maxime, Groh, Adam M. R., Marignier, Romain, Stratton, Jo Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525373/
https://www.ncbi.nlm.nih.gov/pubmed/37771929
http://dx.doi.org/10.3389/fncel.2023.1257000
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author Bigotte, Maxime
Groh, Adam M. R.
Marignier, Romain
Stratton, Jo Anne
author_facet Bigotte, Maxime
Groh, Adam M. R.
Marignier, Romain
Stratton, Jo Anne
author_sort Bigotte, Maxime
collection PubMed
description Ependymal cells make up the epithelial monolayer that lines the brain ventricles and the spinal cord central canal that are filled with cerebrospinal fluid. The ependyma has several functions, including regulating solute exchange between the cerebrospinal fluid and parenchyma, controlling microcirculation of cerebrospinal fluid via coordinated ciliary beating, and acting as a partial barrier. Dysregulation of these functions can lead to waste clearance impairment, cerebrospinal fluid accumulation, hydrocephalus, and more. A role for ependymal cells in a variety of neurological disorders has been proposed, including in neuromyelitis optica and multiple sclerosis, two autoimmune demyelinating diseases of the central nervous system, where periventricular damage is common. What is not known is the mechanisms behind how ependymal cells become dysregulated in these diseases. In neuromyelitis optica, it is well established that autoantibodies directed against Aquaporin-4 are drivers of disease, and it has been shown recently that these autoantibodies can drive ependymal cell dysregulation. We propose a similar mechanism is at play in multiple sclerosis, where autoantibodies targeting a glial cell protein called GlialCAM on ependymal cells are contributing to disease. GlialCAM shares high molecular similarities with the Epstein–Barr virus (EBV) protein EBNA1. EBV has recently been shown to be necessary for multiple sclerosis initiation, yet how EBV mediates pathogenesis, especially in the periventricular area, remains elusive. In this perspective article, we discuss how ependymal cells could be targeted by antibody-related autoimmune mechanisms in autoimmune demyelinating diseases and how this is implicated in ventricular/periventricular pathology.
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spelling pubmed-105253732023-09-28 Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system Bigotte, Maxime Groh, Adam M. R. Marignier, Romain Stratton, Jo Anne Front Cell Neurosci Cellular Neuroscience Ependymal cells make up the epithelial monolayer that lines the brain ventricles and the spinal cord central canal that are filled with cerebrospinal fluid. The ependyma has several functions, including regulating solute exchange between the cerebrospinal fluid and parenchyma, controlling microcirculation of cerebrospinal fluid via coordinated ciliary beating, and acting as a partial barrier. Dysregulation of these functions can lead to waste clearance impairment, cerebrospinal fluid accumulation, hydrocephalus, and more. A role for ependymal cells in a variety of neurological disorders has been proposed, including in neuromyelitis optica and multiple sclerosis, two autoimmune demyelinating diseases of the central nervous system, where periventricular damage is common. What is not known is the mechanisms behind how ependymal cells become dysregulated in these diseases. In neuromyelitis optica, it is well established that autoantibodies directed against Aquaporin-4 are drivers of disease, and it has been shown recently that these autoantibodies can drive ependymal cell dysregulation. We propose a similar mechanism is at play in multiple sclerosis, where autoantibodies targeting a glial cell protein called GlialCAM on ependymal cells are contributing to disease. GlialCAM shares high molecular similarities with the Epstein–Barr virus (EBV) protein EBNA1. EBV has recently been shown to be necessary for multiple sclerosis initiation, yet how EBV mediates pathogenesis, especially in the periventricular area, remains elusive. In this perspective article, we discuss how ependymal cells could be targeted by antibody-related autoimmune mechanisms in autoimmune demyelinating diseases and how this is implicated in ventricular/periventricular pathology. Frontiers Media S.A. 2023-09-13 /pmc/articles/PMC10525373/ /pubmed/37771929 http://dx.doi.org/10.3389/fncel.2023.1257000 Text en Copyright © 2023 Bigotte, Groh, Marignier and Stratton. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Bigotte, Maxime
Groh, Adam M. R.
Marignier, Romain
Stratton, Jo Anne
Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system
title Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system
title_full Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system
title_fullStr Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system
title_full_unstemmed Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system
title_short Pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system
title_sort pathogenic role of autoantibodies at the ependyma in autoimmune disorders of the central nervous system
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525373/
https://www.ncbi.nlm.nih.gov/pubmed/37771929
http://dx.doi.org/10.3389/fncel.2023.1257000
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