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Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis

There has been a growing interest in the presence and role of B cell aggregates within the central nervous system of multiple sclerosis patients. However, very little is known about the expression profile of molecules associated with these aggregates and how they might be influencing aggregate devel...

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Autores principales: Chunder, Rittika, Schropp, Verena, Jabari, Samir, Marzin, Manuel, Amor, Sandra, Kuerten, Stefanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644161/
https://www.ncbi.nlm.nih.gov/pubmed/36389698
http://dx.doi.org/10.3389/fimmu.2022.1025377
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author Chunder, Rittika
Schropp, Verena
Jabari, Samir
Marzin, Manuel
Amor, Sandra
Kuerten, Stefanie
author_facet Chunder, Rittika
Schropp, Verena
Jabari, Samir
Marzin, Manuel
Amor, Sandra
Kuerten, Stefanie
author_sort Chunder, Rittika
collection PubMed
description There has been a growing interest in the presence and role of B cell aggregates within the central nervous system of multiple sclerosis patients. However, very little is known about the expression profile of molecules associated with these aggregates and how they might be influencing aggregate development or persistence in the brain. The current study focuses on the effect of matrix metalloproteinase-3, which is associated with B cell aggregates in autopsied multiple sclerosis brain tissue, on B cells. Autopsied brain sections from multiple sclerosis cases and controls were screened for the presence of CD20(+) B cell aggregates and expression of matrix metalloproteinase-3. Using flow cytometry, enzyme-linked immunosorbent assay and gene array as methods, in vitro studies were conducted using peripheral blood of healthy volunteers to demonstrate the effect of matrix metalloproteinase-3 on B cells. Autopsied brain sections from multiple sclerosis patients containing aggregates of B cells expressed a significantly higher amount of matrix metalloproteinase-3 compared to controls. In vitro experiments demonstrated that matrix metalloproteinase-3 dampened the overall activation status of B cells by downregulating CD69, CD80 and CD86. Furthermore, matrix metalloproteinase-3-treated B cells produced significantly lower amounts of interleukin-6. Gene array data confirmed that matrix metalloproteinase-3 altered the proliferation and survival profiles of B cells. Taken together, out data indicate a role for B cell modulatory properties of matrix metalloproteinase-3.
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spelling pubmed-96441612022-11-15 Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis Chunder, Rittika Schropp, Verena Jabari, Samir Marzin, Manuel Amor, Sandra Kuerten, Stefanie Front Immunol Immunology There has been a growing interest in the presence and role of B cell aggregates within the central nervous system of multiple sclerosis patients. However, very little is known about the expression profile of molecules associated with these aggregates and how they might be influencing aggregate development or persistence in the brain. The current study focuses on the effect of matrix metalloproteinase-3, which is associated with B cell aggregates in autopsied multiple sclerosis brain tissue, on B cells. Autopsied brain sections from multiple sclerosis cases and controls were screened for the presence of CD20(+) B cell aggregates and expression of matrix metalloproteinase-3. Using flow cytometry, enzyme-linked immunosorbent assay and gene array as methods, in vitro studies were conducted using peripheral blood of healthy volunteers to demonstrate the effect of matrix metalloproteinase-3 on B cells. Autopsied brain sections from multiple sclerosis patients containing aggregates of B cells expressed a significantly higher amount of matrix metalloproteinase-3 compared to controls. In vitro experiments demonstrated that matrix metalloproteinase-3 dampened the overall activation status of B cells by downregulating CD69, CD80 and CD86. Furthermore, matrix metalloproteinase-3-treated B cells produced significantly lower amounts of interleukin-6. Gene array data confirmed that matrix metalloproteinase-3 altered the proliferation and survival profiles of B cells. Taken together, out data indicate a role for B cell modulatory properties of matrix metalloproteinase-3. Frontiers Media S.A. 2022-10-26 /pmc/articles/PMC9644161/ /pubmed/36389698 http://dx.doi.org/10.3389/fimmu.2022.1025377 Text en Copyright © 2022 Chunder, Schropp, Jabari, Marzin, Amor and Kuerten 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 Immunology
Chunder, Rittika
Schropp, Verena
Jabari, Samir
Marzin, Manuel
Amor, Sandra
Kuerten, Stefanie
Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis
title Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis
title_full Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis
title_fullStr Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis
title_full_unstemmed Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis
title_short Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis
title_sort identification of a novel role for matrix metalloproteinase-3 in the modulation of b cell responses in multiple sclerosis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9644161/
https://www.ncbi.nlm.nih.gov/pubmed/36389698
http://dx.doi.org/10.3389/fimmu.2022.1025377
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