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  4. A novel neutrophil subset promotes CNS neuron survival and axon regeneration

A novel neutrophil subset promotes CNS neuron survival and axon regeneration

Nat Immunol, 2020 · DOI: 10.1038/s41590-020-00813-0 · Published: December 1, 2020

Regenerative MedicineImmunologyNeurology

Simple Explanation

Transected axons in the central nervous system (CNS) typically fail to regenerate, leading to chronic neurological issues. This study identifies a unique subset of neutrophils that promotes neuron survival and axon regeneration in the CNS. These pro-regenerative neutrophils were found to promote repair in both the optic nerve and spinal cord, suggesting their broad relevance across different areas of the CNS and various neuronal populations. The discovery of these beneficial neutrophils could pave the way for new immunotherapies aimed at reversing CNS damage and restoring neurological function in a range of diseases.

Study Duration
Not specified
Participants
Mice
Evidence Level
Not specified

Key Findings

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    A unique granulocyte subset, characterized as an immature neutrophil, exhibits neuroprotective properties and drives CNS axon regeneration in vivo.
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    These pro-regenerative neutrophils secrete a cocktail of growth factors, contributing to their repair-promoting effects in the optic nerve and spinal cord.
  • 3
    A human cell line with characteristics of immature neutrophils also demonstrates neuroregenerative capacity, suggesting potential clinical translatability.

Research Summary

The study identifies a novel myeloid cell phenotype with neuroprotective and axonogenic properties that arises in the setting of optic nerve and spinal cord injury. This reparative cell is a CD14+Ly6Glow granulocyte with features of an immature neutrophil, which is surprising given the widely held notion that neutrophils infiltrating the CNS are destructive. The neuroprotective and axonogenic properties of the CD14+Ly6Glow cells are, in part, secondary to secretion of the growth factors NGF and IGF-1.

Practical Implications

Therapeutic potential for CNS injuries

The identification of neuroregenerative neutrophils opens avenues for developing novel immunotherapies to treat traumatic brain injury, spinal cord injury, and other CNS disorders.

Targeted Immunomodulation

Strategies to expand endogenous populations of alternatively activated neutrophils or adoptive transfer of ex vivo generated neuroregenerative neutrophils could be explored.

Multimodal therapeutic approaches

Combining the distinctive mechanism of action of Ly6Glow neuroregenerative neutrophil subset with agents that block cell-intrinsic or extrinsic suppressors of axon growth could enhance axonal regeneration.

Study Limitations

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