A new neutrophil subset promotes CNS neuron survival and axon regeneration

Nat Immunol. 2020 Dec;21(12):1496-1505. doi: 10.1038/s41590-020-00813-0. Epub 2020 Oct 26.

Abstract

Transected axons typically fail to regenerate in the central nervous system (CNS), resulting in chronic neurological disability in individuals with traumatic brain or spinal cord injury, glaucoma and ischemia-reperfusion injury of the eye. Although neuroinflammation is often depicted as detrimental, there is growing evidence that alternatively activated, reparative leukocyte subsets and their products can be deployed to improve neurological outcomes. In the current study, we identify a unique granulocyte subset, with characteristics of an immature neutrophil, that had neuroprotective properties and drove CNS axon regeneration in vivo, in part via secretion of a cocktail of growth factors. This pro-regenerative neutrophil promoted repair in the optic nerve and spinal cord, demonstrating its relevance across CNS compartments and neuronal populations. Our findings could ultimately lead to the development of new immunotherapies that reverse CNS damage and restore lost neurological function across a spectrum of diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Biomarkers
  • Cell Communication*
  • Cell Plasticity / immunology
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Central Nervous System / cytology*
  • Central Nervous System / immunology
  • Central Nervous System / metabolism*
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Mice
  • Nerve Regeneration*
  • Neurons / metabolism*
  • Neutrophil Infiltration / immunology
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Optic Nerve / immunology
  • Optic Nerve / metabolism
  • Receptors, Interleukin-8B / metabolism
  • Spinal Cord / cytology
  • Spinal Cord / metabolism
  • Transcriptome
  • Zymosan / metabolism
  • Zymosan / pharmacology

Substances

  • Biomarkers
  • Intercellular Signaling Peptides and Proteins
  • Receptors, Interleukin-8B
  • Zymosan