Abstract
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.
Highlights
Multiple sclerosis (MS) and EAE are inflammatory diseases of the central nervous system (CNS)
We observed a significant decrease in IL-17+ and GM-CSF+ CD4+ T cells in the CNS of
We observed a significant decrease in IL-17+ and GM-CSF+CD4+ T cells in the CNS of CQCQ-treated mice compared with PBS-treated ones (Figure 2D)
Summary
MS and EAE are inflammatory diseases of the CNS. the mechanisms that triggerMS are not fully elucidated, studies in EAE have uncovered the major role played by T cells in disease development, severity, and recovery [1]. MS and EAE are inflammatory diseases of the CNS. Th1 cells and IL-17+ Th17 cells and migrate to the CNS where they induce inflammation and the chemoattraction of myeloid cells [2,3,4,5]. Foxp3-expressing regulatory T (Treg) cells suppress Th1/Th17 cells and overall inflammation through contact-dependent and independent mechanisms [10]. Treg cells were shown to promote remyelination [11,12]. In this context, antigen-presenting cells, such as dendritic cells (DCs), may direct T cell differentiation to Th17/Th1 and Treg cell phenotypes [13,14,15]
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