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Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation
Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are neuroinflammatory diseases of the central nervous system (CNS), where leukocytes and CNS resident cells play important roles in disease development and pathogenesis. The antimalarial drug chloroquine (CQ) has been shown...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349328/ https://www.ncbi.nlm.nih.gov/pubmed/32516999 http://dx.doi.org/10.3390/brainsci10060348 |
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author | Thome, Rodolfo Boehm, Alexandra Ishikawa, Larissa Lumi Watanabe Casella, Giacomo Munhoz, Jaqueline Ciric, Bogoljub Zhang, Guang-Xian Rostami, Abdolmohamad |
author_facet | Thome, Rodolfo Boehm, Alexandra Ishikawa, Larissa Lumi Watanabe Casella, Giacomo Munhoz, Jaqueline Ciric, Bogoljub Zhang, Guang-Xian Rostami, Abdolmohamad |
author_sort | Thome, Rodolfo |
collection | PubMed |
description | Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are neuroinflammatory diseases of the central nervous system (CNS), where leukocytes and CNS resident cells play important roles in disease development and pathogenesis. The antimalarial drug chloroquine (CQ) has been shown to suppress EAE by modulating dendritic cells (DCs) and Th17 cells. However, the mechanism of action by which CQ modulates EAE is far from being elucidated. Here, we comprehensively analyzed the CNS of CQ and PBS-treated EAE mice to identify and characterize the cells that are affected by CQ. Our results show that leukocytes are largely modulated by CQ and have a reduction in the expression of inflammatory markers. Intriguingly, CQ vastly modulated the CNS resident cells astrocytes, oligodendrocytes (OLs) and microglia (MG), with the latter producing IL-10 and IL-12p70. Overall, our results show a panoramic view of the cellular components that are affect by CQ and provide further evidence that drug repurposing of CQ will be beneficial to MS patients. |
format | Online Article Text |
id | pubmed-7349328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73493282020-07-22 Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation Thome, Rodolfo Boehm, Alexandra Ishikawa, Larissa Lumi Watanabe Casella, Giacomo Munhoz, Jaqueline Ciric, Bogoljub Zhang, Guang-Xian Rostami, Abdolmohamad Brain Sci Article Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are neuroinflammatory diseases of the central nervous system (CNS), where leukocytes and CNS resident cells play important roles in disease development and pathogenesis. The antimalarial drug chloroquine (CQ) has been shown to suppress EAE by modulating dendritic cells (DCs) and Th17 cells. However, the mechanism of action by which CQ modulates EAE is far from being elucidated. Here, we comprehensively analyzed the CNS of CQ and PBS-treated EAE mice to identify and characterize the cells that are affected by CQ. Our results show that leukocytes are largely modulated by CQ and have a reduction in the expression of inflammatory markers. Intriguingly, CQ vastly modulated the CNS resident cells astrocytes, oligodendrocytes (OLs) and microglia (MG), with the latter producing IL-10 and IL-12p70. Overall, our results show a panoramic view of the cellular components that are affect by CQ and provide further evidence that drug repurposing of CQ will be beneficial to MS patients. MDPI 2020-06-05 /pmc/articles/PMC7349328/ /pubmed/32516999 http://dx.doi.org/10.3390/brainsci10060348 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Thome, Rodolfo Boehm, Alexandra Ishikawa, Larissa Lumi Watanabe Casella, Giacomo Munhoz, Jaqueline Ciric, Bogoljub Zhang, Guang-Xian Rostami, Abdolmohamad Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation |
title | Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation |
title_full | Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation |
title_fullStr | Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation |
title_full_unstemmed | Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation |
title_short | Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation |
title_sort | comprehensive analysis of the immune and stromal compartments of the cns in eae mice reveal pathways by which chloroquine suppresses neuroinflammation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349328/ https://www.ncbi.nlm.nih.gov/pubmed/32516999 http://dx.doi.org/10.3390/brainsci10060348 |
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