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Cortical CD200-CD200R and CD47-SIRPα expression is associated with multiple sclerosis pathology
Aletta M R van den Bosch1, Dennis Wever1, Pleun Schonewille1
1Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Amsterdam, 1105 BA, The Netherlands.
Brain Communications
|August 23, 2024
Summary
In multiple sclerosis (MS), reduced CD200 expression in normal-appearing grey matter may drive grey matter lesion formation. Targeting CD200 pathways could mitigate MS pathology in both white and grey matter.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Multiple Sclerosis Pathogenesis
Background:
- Microglial activity is crucial for brain homeostasis, regulated by CD200-CD200R and CD47-SIRPα signaling pathways.
- Altered microglial control is suspected in multiple sclerosis (MS) pathogenesis, particularly within grey matter (GM) and white matter (WM).
Purpose of the Study:
- To investigate the expression of CD200, CD47, CD200R, and SIRPα in various MS brain tissues compared to controls.
- To explore the potential role of altered microglial regulatory pathways in MS, focusing on grey matter lesions and normal-appearing tissues.
Main Methods:
- Quantitative PCR (qPCR) and immunohistochemistry were employed to assess gene and protein expression.
- Analysis included normal-appearing cortical grey matter (NAGM), normal-appearing white matter (NAWM), GM lesions, perilesional GM, and control brain tissue.
Main Results:
- CD200 expression was lower in MS NAGM, particularly in cortical layers 1 and 2, and correlated negatively with cortical lesion rate.
- CD200 and CD47 expression were reduced in GM lesions compared to NAGM and perilesional GM.
- CD200R expression was lower in MS NAGM, while SIRPα expression increased in and around GM lesions.
Conclusions:
- CD200 and CD47 signaling pathways are implicated in multiple sclerosis grey matter lesion formation and progression.
- Modulating CD200 pathways presents a potential therapeutic strategy to reduce MS pathology in both white and grey matter.
