Abstract
Multiple sclerosis (MS) is an inflammatory disease in which myelin in the spinal cord is damaged. C-C chemokine receptor type 5 (CCR5) is implicated in immune cell migration and cytokine release in central nervous system (CNS). We investigated whether CCR5 plays a role in MS progression using a murine model, experimental autoimmune encephalomyelitis (EAE), in CCR5 deficient (CCR5−/−) mice. CCR5−/− and CCR5+/+ (wild-type) mice were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) followed by pertussis toxin, after which EAE paralysis was scored for 28 days. We found that clinical scoring and EAE neuropathology were lower in CCR5−/− mice than CCR5+/+ mice. Immune cells (CD3+, CD4+, CD8+, B cell, NK cell and macrophages) infiltration and astrocytes/microglial activation were attenuated in CCR5−/− mice. Moreover, levels of IL-1β, TNF-α, IFN-γ and MCP-1 cytokine levels were decreased in CCR5−/− mice spinal cord. Myelin basic protein (MBP) and CNPase were increased while NG2 and O4 were decreased in CCR5−/− mice, indicating that demyelination was suppressed by CCR5 gene deletion. These findings suggest that CCR5 is likely participating in demyelination in the spinal cord the MS development, and that it could serve as an effective therapeutic target for the treatment of MS.
Highlights
The autoimmune response in the central nervous system (CNS) plays a critical role in chronic inflammation and demyelination in human multiple sclerosis (MS) and in the animal model, experimental autoimmune encephalomyelitis (EAE) [1]
Monocyte chemotactic protein 1 (MCP-1) is unregulated Th1 immune responses during the acute phase of disease induced by myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) or other encephalitogenic antigens [14,15,16]
chemokine receptor type 5 (CCR5)+/+ and CCR5-/- mice sensitized at 8 weeks of age developed clinical signs of MOG35-55 peptide-induced EAE
Summary
The autoimmune response in the central nervous system (CNS) plays a critical role in chronic inflammation and demyelination in human multiple sclerosis (MS) and in the animal model, experimental autoimmune encephalomyelitis (EAE) [1]. EAE is widely used as and animal model of human CNS demyelinating diseases, including MS [2]. It is mediated by activated myelin antigen-specific CD4+ Th1 cells and is characterized histologically by Ag-specific and nonspecific CD4+ and CD8+ Th1 cell infiltration [3]. Interleukin-1 (IL-1) is produced by a variety of cells, such as monocytes/ macrophages, epithelial and endothelial cells and glial cells [12] These cytokine plays a crucial role in leukocyte extravasation into inflammatory sites through upregulation of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 [13]. Our previous study found that MCP-1 levels were significantly reduced in lung tumor tissue and blood in CCR5-deficient mice compared with controls [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
