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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Main Authors: Rodolfo Thome, Alexandra Boehm, Larissa Lumi Watanabe Ishikawa, Giacomo Casella, Jaqueline Munhoz, Bogoljub Ciric, Guang-Xian Zhang, Abdolmohamad Rostami
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Brain Sciences
Subjects:
EAE
Online Access:https://www.mdpi.com/2076-3425/10/6/348
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spelling doaj-bf8aeb3cf34c4d209953f8a0530519832020-11-25T02:35:59ZengMDPI AGBrain Sciences2076-34252020-06-011034834810.3390/brainsci10060348Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses NeuroinflammationRodolfo Thome0Alexandra Boehm1Larissa Lumi Watanabe Ishikawa2Giacomo Casella3Jaqueline Munhoz4Bogoljub Ciric5Guang-Xian Zhang6Abdolmohamad Rostami7Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USAMultiple 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.https://www.mdpi.com/2076-3425/10/6/348chloroquineEAEdendritic cellsmicrogliaastrocytesoligodendrocytes
collection DOAJ
language English
format Article
sources DOAJ
author Rodolfo Thome
Alexandra Boehm
Larissa Lumi Watanabe Ishikawa
Giacomo Casella
Jaqueline Munhoz
Bogoljub Ciric
Guang-Xian Zhang
Abdolmohamad Rostami
spellingShingle Rodolfo Thome
Alexandra Boehm
Larissa Lumi Watanabe Ishikawa
Giacomo Casella
Jaqueline Munhoz
Bogoljub Ciric
Guang-Xian Zhang
Abdolmohamad Rostami
Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation
Brain Sciences
chloroquine
EAE
dendritic cells
microglia
astrocytes
oligodendrocytes
author_facet Rodolfo Thome
Alexandra Boehm
Larissa Lumi Watanabe Ishikawa
Giacomo Casella
Jaqueline Munhoz
Bogoljub Ciric
Guang-Xian Zhang
Abdolmohamad Rostami
author_sort Rodolfo Thome
title 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_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_sort comprehensive analysis of the immune and stromal compartments of the cns in eae mice reveal pathways by which chloroquine suppresses neuroinflammation
publisher MDPI AG
series Brain Sciences
issn 2076-3425
publishDate 2020-06-01
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.
topic chloroquine
EAE
dendritic cells
microglia
astrocytes
oligodendrocytes
url https://www.mdpi.com/2076-3425/10/6/348
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