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Contribution of LTi and T(H)17 cells to B cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis
BACKGROUND: In a subgroup of patients suffering from progressive multiple sclerosis (MS), which is an inflammation-mediated neurodegenerative disease of the central nervous system (CNS), B cell aggregates were discovered within the meninges. Occurrence of these structures was associated with a more...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540524/ https://www.ncbi.nlm.nih.gov/pubmed/31138214 http://dx.doi.org/10.1186/s12974-019-1500-x |
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author | Schropp, Verena Rohde, Jörn Rovituso, Damiano M. Jabari, Samir Bharti, Richa Kuerten, Stefanie |
author_facet | Schropp, Verena Rohde, Jörn Rovituso, Damiano M. Jabari, Samir Bharti, Richa Kuerten, Stefanie |
author_sort | Schropp, Verena |
collection | PubMed |
description | BACKGROUND: In a subgroup of patients suffering from progressive multiple sclerosis (MS), which is an inflammation-mediated neurodegenerative disease of the central nervous system (CNS), B cell aggregates were discovered within the meninges. Occurrence of these structures was associated with a more severe disease course and cortical histopathology. We have developed the B cell-dependent MP4-induced experimental autoimmune encephalomyelitis (EAE) as a mouse model to mimic this trait of the human disease. The aim of this study was to determine a potential role of lymphoid tissue inducer (LTi) and T(H)17 cells in the process of B cell aggregate formation in the MP4 model. METHODS: We performed flow cytometry of cerebellar and splenic tissue of MP4-immunized mice in the acute and chronic stage of the disease to analyze the presence of CD3(−)CD5(−)CD4(+)RORγt(+) LTi and CD3(+)CD5(+)CD4(+)RORγt(+) T(H)17 cells. Myelin oligodendrocyte glycoprotein (MOG):35–55-induced EAE was used as B cell-independent control model. We further determined the gene expression profile of B cell aggregates using laser capture microdissection, followed by RNA sequencing. RESULTS: While we were able to detect LTi cells in the embryonic spleen and adult intestine, which served as positive controls, there was no evidence for the existence of such a population in acute or chronic EAE in neither of the two models. Yet, we detected CD3(−)CD5(−)CD4(−)RORγt(+) innate lymphoid cells (ILCs) and T(H)17 cells in the CNS, the latter especially in the chronic stage of MP4-induced EAE. Moreover, we observed a unique gene signature in CNS B cell aggregates compared to draining lymph nodes of MP4-immunized mice and to cerebellum as well as draining lymph nodes of mice with MOG:35–55-induced EAE. CONCLUSION: The absence of LTi cells in the cerebellum suggests that other cells might take over the function as an initiator of lymphoid tissue formation in the CNS. Overall, the development of ectopic lymphoid organs is a complex process based on an interplay between several molecules and signals. Here, we propose some potential candidates, which might be involved in the formation of B cell aggregates in the CNS of MP4-immunized mice. |
format | Online Article Text |
id | pubmed-6540524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-65405242019-06-03 Contribution of LTi and T(H)17 cells to B cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis Schropp, Verena Rohde, Jörn Rovituso, Damiano M. Jabari, Samir Bharti, Richa Kuerten, Stefanie J Neuroinflammation Research BACKGROUND: In a subgroup of patients suffering from progressive multiple sclerosis (MS), which is an inflammation-mediated neurodegenerative disease of the central nervous system (CNS), B cell aggregates were discovered within the meninges. Occurrence of these structures was associated with a more severe disease course and cortical histopathology. We have developed the B cell-dependent MP4-induced experimental autoimmune encephalomyelitis (EAE) as a mouse model to mimic this trait of the human disease. The aim of this study was to determine a potential role of lymphoid tissue inducer (LTi) and T(H)17 cells in the process of B cell aggregate formation in the MP4 model. METHODS: We performed flow cytometry of cerebellar and splenic tissue of MP4-immunized mice in the acute and chronic stage of the disease to analyze the presence of CD3(−)CD5(−)CD4(+)RORγt(+) LTi and CD3(+)CD5(+)CD4(+)RORγt(+) T(H)17 cells. Myelin oligodendrocyte glycoprotein (MOG):35–55-induced EAE was used as B cell-independent control model. We further determined the gene expression profile of B cell aggregates using laser capture microdissection, followed by RNA sequencing. RESULTS: While we were able to detect LTi cells in the embryonic spleen and adult intestine, which served as positive controls, there was no evidence for the existence of such a population in acute or chronic EAE in neither of the two models. Yet, we detected CD3(−)CD5(−)CD4(−)RORγt(+) innate lymphoid cells (ILCs) and T(H)17 cells in the CNS, the latter especially in the chronic stage of MP4-induced EAE. Moreover, we observed a unique gene signature in CNS B cell aggregates compared to draining lymph nodes of MP4-immunized mice and to cerebellum as well as draining lymph nodes of mice with MOG:35–55-induced EAE. CONCLUSION: The absence of LTi cells in the cerebellum suggests that other cells might take over the function as an initiator of lymphoid tissue formation in the CNS. Overall, the development of ectopic lymphoid organs is a complex process based on an interplay between several molecules and signals. Here, we propose some potential candidates, which might be involved in the formation of B cell aggregates in the CNS of MP4-immunized mice. BioMed Central 2019-05-28 /pmc/articles/PMC6540524/ /pubmed/31138214 http://dx.doi.org/10.1186/s12974-019-1500-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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. |
spellingShingle | Research Schropp, Verena Rohde, Jörn Rovituso, Damiano M. Jabari, Samir Bharti, Richa Kuerten, Stefanie Contribution of LTi and T(H)17 cells to B cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis |
title | Contribution of LTi and T(H)17 cells to B cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis |
title_full | Contribution of LTi and T(H)17 cells to B cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis |
title_fullStr | Contribution of LTi and T(H)17 cells to B cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis |
title_full_unstemmed | Contribution of LTi and T(H)17 cells to B cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis |
title_short | Contribution of LTi and T(H)17 cells to B cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis |
title_sort | contribution of lti and t(h)17 cells to b cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540524/ https://www.ncbi.nlm.nih.gov/pubmed/31138214 http://dx.doi.org/10.1186/s12974-019-1500-x |
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