Related Experiment Video
Updated: Dec 13, 2025
Assessing Microglial Phagocytosis of Myelin Debris in vitro Under Repeated Magnetic Stimulation
Published on: June 17, 2025
CD36-mediated uptake of myelin debris by macrophages and microglia reduces neuroinflammation
Elien Grajchen1, Elien Wouters1, Britt van de Haterd1
1Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium.
Background:
The presence of foamy macrophages and microglia containing intracellular myelin remnants is a pathological hallmark of neurodegenerative disorders such as multiple sclerosis (MS). Despite the importance of myelin internalization in affecting both central nervous system repair and neuroinflammation, the receptors involved in myelin clearance and their impact on the phagocyte phenotype and lesion progression remain to be clarified.
Methods:
Flow cytometry, quantitative PCR, and immunohistochemistry were used to define the mRNA and protein abundance of CD36 in myelin-containing phagocytes. The impact of CD36 and nuclear factor erythroid 2-related factor 2 (NRF2) on the phagocytic and inflammatory features of macrophages and microglia was assessed using a pharmacological CD36 inhibitor (sulfo-N-succinimidyl oleate) and Nrf2-/- bone marrow-derived macrophages. Finally, the experimental autoimmune encephalomyelitis (EAE) model was used to establish the impact of CD36 inhibition on neuroinflammation and myelin phagocytosis in vivo.
Results:
Here, we show that the fatty acid translocase CD36 is required for the uptake of myelin debris by macrophages and microglia, and that myelin internalization increased CD36 expression through NRF2. Pharmacological inhibition of CD36 promoted the inflammatory properties of myelin-containing macrophages and microglia in vitro, which was paralleled by a reduced activity of the anti-inflammatory lipid-sensing liver X receptors and peroxisome proliferator-activated receptors. By using the EAE model, we provide evidence that CD36 is essential for myelin debris clearance in vivo. Importantly, CD36 inhibition markedly increased the neuroinflammatory burden and disease severity in the EAE model.
Conclusion:
Altogether, we show for the first time that CD36 is crucial for clearing myelin debris and suppressing neuroinflammation in demyelinating disorders such as MS.
Insights
CD36 is essential for clearing myelin debris in neurodegenerative diseases like MS. Inhibiting CD36 worsens neuroinflammation and disease severity, highlighting its critical role in myelin clearance and immune regulation.
Area of Science:
- Neuroimmunology
- Cellular Biology
- Neurodegeneration
Background:
- Foamy macrophages and microglia with myelin remnants characterize neurodegenerative disorders like multiple sclerosis (MS).
- Myelin clearance is vital for central nervous system repair and modulating neuroinflammation.
- Receptors mediating myelin uptake and their effects on phagocyte phenotype and disease progression require further investigation.
Purpose of the Study:
- To investigate the role of CD36 in myelin debris uptake by macrophages and microglia.
- To determine the impact of CD36 and NRF2 on phagocytic and inflammatory functions of myeloid cells.
- To evaluate the in vivo effects of CD36 inhibition on neuroinflammation and myelin clearance in a disease model.
Main Methods:
- Utilized flow cytometry, qPCR, and immunohistochemistry to quantify CD36 expression.
- Employed a CD36 inhibitor and Nrf2 knockout macrophages to assess phagocytic and inflammatory responses.
- Investigated the effects of CD36 inhibition in the experimental autoimmune encephalomyelitis (EAE) model.
Main Results:
- CD36 mediates the uptake of myelin debris by macrophages and microglia, with expression upregulated by myelin via NRF2.
- Pharmacological CD36 inhibition enhanced inflammatory properties of phagocytes and reduced anti-inflammatory receptor activity.
- In vivo EAE model demonstrated CD36's essential role in myelin clearance, with inhibition exacerbating neuroinflammation and disease severity.
Conclusions:
- CD36 is crucial for efficient myelin debris clearance in demyelinating diseases.
- CD36 plays a significant role in suppressing neuroinflammation in conditions such as MS.
- Targeting CD36 may offer therapeutic potential for managing demyelinating disorders.
