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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...

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Autores principales: Thome, Rodolfo, Boehm, Alexandra, Ishikawa, Larissa Lumi Watanabe, Casella, Giacomo, Munhoz, Jaqueline, Ciric, Bogoljub, Zhang, Guang-Xian, Rostami, Abdolmohamad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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