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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.
Abstract:
Control of microglia activity through CD200-CD200R and CD47-SIRPα interactions has been implicated in brain homeostasis. Here, we assessed CD200, CD47, CD200R and SIRPα expression with qPCR and immunohistochemistry in multiple sclerosis (MS) normal-appearing cortical grey matter (NAGM), normal-appearing white matter (NAWM), cortical grey matter (GM) lesions and perilesional GM, and compared this to control GM and white matter (WM), to investigate possible altered control of microglia in MS. In MS NAGM, CD200 expression is lower compared with control GM, specifically in cortical layers 1 and 2, and CD200 expression in NAGM negatively correlates with the cortical lesion rate. Interestingly, NAGM and NAWM CD200 expression is positively correlated, and NAGM CD200 expression negatively correlates with the proportion of active and mixed WM lesions. In GM lesions, CD200 and CD47 expressions are lower compared with NAGM and perilesional GM. CD200R expression is lower in MS NAGM, whereas SIRPα was increased in and around GM lesions. Taken together, our data indicate that CD200 and CD47 play a role in GM MS lesion formation and progression, respectively, and that targeting CD200 pathways may offer therapeutic avenues to mitigate MS pathology in both WM and GM.
Insights
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.
