Deletion of CD47 from Schwann cells and macrophages hastens myelin disruption/ dismantling and scavenging in Schwann cells and augments myelin debris phagocytosis in macrophages

Journal of Neuroinflammation, 2023 · DOI: https://doi.org/10.1186/s12974-023-02929-0 · Published: October 10, 2023

Immunology Regenerative Medicine & Stem Cells

Simple Explanation

Myelin, which insulates nerve fibers, can break down due to injury or disease. The resulting debris can hinder repair unless it's efficiently cleared away by cells like Schwann cells and macrophages. This study found that CD47, a protein on the surface of Schwann cells and macrophages, actually inhibits the breakdown and removal of myelin debris. By deleting CD47 in mice, researchers observed faster myelin clearance, axon regeneration, and functional recovery after nerve injury, suggesting CD47 plays an inhibitory role.

Study Duration

Not specified

Participants

CD47 null (CD47−/−) and wild type mice

Evidence Level

In vivo study

Key Findings

1
Myelin debris clearance, axon regeneration, and function recovery were all faster in CD47−/− mice than in wild type mice.
2
CD47-deleted Schwann cells displayed enhanced disruption/dismantling and scavenging of myelin in CD47−/− mice.
3
CD47-deleted macrophages from CD47−/− mice phagocytosed more myelin debris than CD47-expressing phagocytes from wild type mice.

Research Summary

This study reveals two novel normally occurring CD47-dependent mechanisms that impede myelin debris clearance by acting as a cell surface receptor. First, CD47 on Schwann cells inhibits myelin disruption/dismantling and myelin debris scavenging in Schwann cells. Second, CD47 expressed on macrophages inhibits myelin debris phagocytosis in macrophages.

Practical Implications

Therapeutic Target

Targeting CD47 could enhance myelin debris clearance and promote recovery in nerve injuries and demyelinating diseases.

Understanding Neurodegenerative Diseases

CD47's role in inhibiting phagocytosis may contribute to the delayed myelin debris clearance observed in multiple sclerosis and spinal cord injuries.

Broader Implications for Phagocytosis

The inhibitory mechanisms of CD47 on phagocytosis may apply to other cellular targets, such as red blood cells, platelets, and tumor cells.

Study Limitations

1
The molecular mechanism by which CD47 delayed myelin disruption/dismantling and debris scavenging needs verification.
2
The exact molecular mechanism by which CD47 on phagocytes could have inhibited phagocytosis needs verification.
3
A point of consideration is whether genetic deletion of CD47 from myelin in CD47−/− mice could have affected the expression of other myelin molecule(s)

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