Comprehensive Analysis of the Immune and Stromal Compartments of the CNS in EAE Mice Reveal Pathways by Which Chloroquine Suppresses Neuroinflammation

Brain Sciences

Abdolmohamad Rostami¹  Guang-Xian Zhang¹  LarissaLumi Watanabe Ishikawa¹  Alexandra Boehm¹  Giacomo Casella¹  Jaqueline Munhoz¹  Rodolfo Thome¹  Bogoljub Ciric¹ 

[1] Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA;

关键词: chloroquine;    EAE;    dendritic cells;    microglia;    astrocytes;    oligodendrocytes;   

DOI  :  10.3390/brainsci10060348

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown