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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...

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Autores principales: Schropp, Verena, Rohde, Jörn, Rovituso, Damiano M., Jabari, Samir, Bharti, Richa, Kuerten, Stefanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
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.
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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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