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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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 |
work_keys_str_mv |
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