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

Microglia/immunology
Microglia/metabolism
Inflammation/immunology
Inflammation/metabolism
Zebrafish*
Tumor Necrosis Factor-alpha/metabolism
Animals
Neutrophils*/immunology
Neutrophils*/metabolism
Spinal Cord*/immunology
Spinal Cord*/metabolism
Receptors, CXCR4/metabolism
Macrophages/immunology
Macrophages/metabolism
Neutrophil Infiltration/physiology
Spinal Cord Injuries*/immunology
Spinal Cord Injuries*/metabolism
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism
Spinal Cord Regeneration*/physiology

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.

Genes / Markers

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