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Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes
Recent genome-wide association studies have identified over 230 genetic risk loci for multiple sclerosis. Current experimental autoimmune encephalomyelitis (EAE) models requiring active induction of disease may not be optimally suited for the characterization of the function of these genes. We have...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531036/ https://www.ncbi.nlm.nih.gov/pubmed/33072080 http://dx.doi.org/10.3389/fimmu.2020.02165 |
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author | Faber, Hans Kurtoic, Dunja Krishnamoorthy, Gurumoorthy Weber, Peter Pütz, Benno Müller-Myhsok, Bertram Weber, Frank Andlauer, Till F. M. |
author_facet | Faber, Hans Kurtoic, Dunja Krishnamoorthy, Gurumoorthy Weber, Peter Pütz, Benno Müller-Myhsok, Bertram Weber, Frank Andlauer, Till F. M. |
author_sort | Faber, Hans |
collection | PubMed |
description | Recent genome-wide association studies have identified over 230 genetic risk loci for multiple sclerosis. Current experimental autoimmune encephalomyelitis (EAE) models requiring active induction of disease may not be optimally suited for the characterization of the function of these genes. We have thus used gene expression profiling to study whether spontaneous opticospinal EAE (OSE) or MOG-induced EAE mirrors the genetic contribution to the pathogenesis of multiple sclerosis more faithfully. To this end, we compared gene expression in OSE and MOG EAE models and analyzed the relationship of both models to human multiple sclerosis risk genes and T helper cell biology. We observed stronger gene expression changes and an involvement of more pathways of the adaptive immune system in OSE than MOG EAE. Furthermore, we demonstrated a more extensive enrichment of human MS risk genes among transcripts differentially expressed in OSE than was the case for MOG EAE. Transcripts differentially expressed only in diseased OSE mice but not in MOG EAE were significantly enriched for T helper cell-specific transcripts. These transcripts are part of immune-regulatory pathways. The activation of the adaptive immune system and the enrichment of both human multiple sclerosis risk genes and T helper cell-specific transcripts were also observed in OSE mice showing only mild disease signs. These expression changes may, therefore, be indicative of processes at disease onset. In summary, more human multiple sclerosis risk genes were differentially expressed in OSE than was observed for MOG EAE, especially in T(H)1 cells. When studying the functional role of multiple sclerosis risk genes and pathways during disease onset and their interactions with the environment, spontaneous OSE may thus show advantages over MOG-induced EAE. |
format | Online Article Text |
id | pubmed-7531036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75310362020-10-17 Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes Faber, Hans Kurtoic, Dunja Krishnamoorthy, Gurumoorthy Weber, Peter Pütz, Benno Müller-Myhsok, Bertram Weber, Frank Andlauer, Till F. M. Front Immunol Immunology Recent genome-wide association studies have identified over 230 genetic risk loci for multiple sclerosis. Current experimental autoimmune encephalomyelitis (EAE) models requiring active induction of disease may not be optimally suited for the characterization of the function of these genes. We have thus used gene expression profiling to study whether spontaneous opticospinal EAE (OSE) or MOG-induced EAE mirrors the genetic contribution to the pathogenesis of multiple sclerosis more faithfully. To this end, we compared gene expression in OSE and MOG EAE models and analyzed the relationship of both models to human multiple sclerosis risk genes and T helper cell biology. We observed stronger gene expression changes and an involvement of more pathways of the adaptive immune system in OSE than MOG EAE. Furthermore, we demonstrated a more extensive enrichment of human MS risk genes among transcripts differentially expressed in OSE than was the case for MOG EAE. Transcripts differentially expressed only in diseased OSE mice but not in MOG EAE were significantly enriched for T helper cell-specific transcripts. These transcripts are part of immune-regulatory pathways. The activation of the adaptive immune system and the enrichment of both human multiple sclerosis risk genes and T helper cell-specific transcripts were also observed in OSE mice showing only mild disease signs. These expression changes may, therefore, be indicative of processes at disease onset. In summary, more human multiple sclerosis risk genes were differentially expressed in OSE than was observed for MOG EAE, especially in T(H)1 cells. When studying the functional role of multiple sclerosis risk genes and pathways during disease onset and their interactions with the environment, spontaneous OSE may thus show advantages over MOG-induced EAE. Frontiers Media S.A. 2020-09-18 /pmc/articles/PMC7531036/ /pubmed/33072080 http://dx.doi.org/10.3389/fimmu.2020.02165 Text en Copyright © 2020 Faber, Kurtoic, Krishnamoorthy, Weber, Pütz, Müller-Myhsok, Weber and Andlauer. http://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 Faber, Hans Kurtoic, Dunja Krishnamoorthy, Gurumoorthy Weber, Peter Pütz, Benno Müller-Myhsok, Bertram Weber, Frank Andlauer, Till F. M. Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes |
title | Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes |
title_full | Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes |
title_fullStr | Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes |
title_full_unstemmed | Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes |
title_short | Gene Expression in Spontaneous Experimental Autoimmune Encephalomyelitis Is Linked to Human Multiple Sclerosis Risk Genes |
title_sort | gene expression in spontaneous experimental autoimmune encephalomyelitis is linked to human multiple sclerosis risk genes |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531036/ https://www.ncbi.nlm.nih.gov/pubmed/33072080 http://dx.doi.org/10.3389/fimmu.2020.02165 |
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