Elevated phagocytic capacity directs innate spinal cord repair

Area of Science:

• Neuroscience
• Immunology
• Regenerative Medicine

Background:

• Spinal cord injury (SCI) in mammals leads to chronic inflammation and inefficient debris clearance, hindering recovery.
• Immune cell responses after SCI are complex, with pro-regenerative functions often overshadowed by detrimental inflammatory states.

Purpose of the Study:

• To investigate the differences in immune responses to SCI between zebrafish and mammals.
• To identify molecular mechanisms underlying efficient spinal cord regeneration in zebrafish.

Main Methods:

• Single-cell transcriptomics to analyze immune cell states after SCI in zebrafish.
• Inducible genetic ablation to study the function of specific genes in zebrafish macrophages.
• Cross-species comparative analysis to identify conserved and divergent genes.

Main Results:

• Zebrafish exhibit transient immune activation and efficient debris clearance post-SCI, promoting regeneration.
• Zebrafish macrophages are highly phagocytic and essential for spinal cord repair.
• The gene transcription and immune response regulator (tcim) was identified as a key regulator of macrophage phagocytosis and regeneration in zebrafish.
• Expression of human TCIM in zebrafish accelerated debris clearance and regeneration by enhancing myeloid precursor function.

Conclusions:

• Elevated phagocytic capacity is a central requirement for innate spinal cord repair.
• Targeting tcim or enhancing phagocytosis presents a potential therapeutic strategy for spinal cord injury.