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bioRxiv · 10.1101/2024.06.11.598515

Elevated phagocytic capacity directs innate spinal cord repair

Shaw, D. K.·Saraswathy, V. M.·McAdow, A. R.·Zhou, L.·Park, D.·Mote, R.·Johnson, A. N.·Mokalled, M. H.
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Abstract

Immune cells elicit a continuum of transcriptional and functional states after spinal cord injury (SCI). In mammals, inefficient debris clearance and chronic inflammation impede recovery and overshadow pro-regenerative immune functions. We found that, unlike mammals, zebrafish SCI elicits transient immune activation and efficient debris clearance, without causing chronic inflammation. Single-cell transcriptomics and inducible genetic ablation showed zebrafish macrophages are highly phagocytic and required for regeneration. Cross-species comparisons between zebrafish and mammalian macrophages identified transcription and immune response regulator (tcim) as a macrophage-enriched zebrafish gene. Genetic deletion of zebrafish tcim impairs phagocytosis and regeneration, causes aberrant and chronic immune activation, and can be rescued by transplanting wild-type immune precursors into tcim mutants. Conversely, genetic expression of human TCIM accelerates debris clearance and regeneration by reprogramming myeloid precursors into activated phagocytes. This study establishes a central requirement for elevated phagocytic capacity to achieve innate spinal cord repair.

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Shaw, D. K., Saraswathy, V. M., McAdow, A. R., Zhou, L., Park, D., Mote, R., Johnson, A. N., Mokalled, M. H.. 2024-06-13. Elevated phagocytic capacity directs innate spinal cord repair. https://doi.org/10.1101/2024.06.11.598515

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