PUBLICATION

Neutrophil immune profile guides spinal cord regeneration in zebrafish

Authors
de Sena-Tomás, C., Rebola Lameira, L., Rebocho da Costa, M., Naique Taborda, P., Laborde, A., Orger, M., de Oliveira, S., Saúde, L.
ID
ZDB-PUB-240627-17
Date
2024
Source
Brain, behavior, and immunity   120: 514-531 (Journal)
Registered Authors
de Oliveira, Sofia, Orger, Mike
Keywords
Macrophage, Microglia, Neutrophils, Reverse migration, Spinal cord regeneration, Zebrafish
Datasets
GEO:GSE271113
MeSH Terms
  • Animals
  • Inflammation/immunology
  • Inflammation/metabolism
  • Macrophages/immunology
  • Macrophages/metabolism
  • Microglia/immunology
  • Microglia/metabolism
  • Neutrophil Infiltration/physiology
  • Neutrophils*/immunology
  • Neutrophils*/metabolism
  • Receptors, CXCR4/metabolism
  • Spinal Cord*/immunology
  • Spinal Cord*/metabolism
  • Spinal Cord Injuries*/immunology
  • Spinal Cord Injuries*/metabolism
  • Spinal Cord Regeneration*/physiology
  • Tumor Necrosis Factor-alpha/metabolism
  • Zebrafish*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
38925414 Full text @ Brain Behav. Immun.
Abstract
Spinal cord injury triggers a strong innate inflammatory response in both non-regenerative mammals and regenerative zebrafish. Neutrophils are the first immune population to be recruited to the injury site. Yet, their role in the repair process, particularly in a regenerative context, remains largely unknown. Here, we show that, following rapid recruitment to the injured spinal cord, neutrophils mostly reverse migrate throughout the zebrafish body. In addition, promoting neutrophil inflammation resolution by inhibiting Cxcr4 boosts cellular and functional regeneration. Neutrophil-specific RNA-seq analysis reveals an enhanced activation state that correlates with a transient increase in tnf-α expression in macrophage/microglia populations. Conversely, blocking neutrophil recruitment through Cxcr1/2 inhibition diminishes the presence of macrophage/microglia at the injury site and impairs spinal cord regeneration. Altogether, these findings provide new insights into the role of neutrophils in spinal cord regeneration, emphasizing the significant impact of their immune profile on the outcome of the repair process.
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