Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery

Journal of Neuroinflammation, 2025 · DOI: https://doi.org/10.1186/s12974-025-03362-1 · Published: January 27, 2025

Simple Explanation

This study investigates the role of a protein called C/EBPβ in spinal cord injury (SCI). It finds that C/EBPβ is increased in immune cells called microglia after SCI, contributing to inflammation. The researchers discovered that C/EBPβ promotes a specific type of cell death called pyroptosis in microglia. This pyroptosis leads to the release of inflammatory substances that harm nerve cells and hinder recovery after SCI. By blocking C/EBPβ or inhibiting pyroptosis, the study showed reduced inflammation, nerve cell death, and improved neurological recovery in mice with SCI. This suggests that targeting C/EBPβ could be a potential treatment strategy for SCI.

Study Duration

Not specified

Participants

165 adult C57BL/6J mice

Evidence Level

Level 1, In-vivo and In-vitro experiments

Key Findings

1
C/EBPβ is significantly upregulated in microglia after spinal cord injury in mice and is associated with neuroinflammation.
2
C/EBPβ promotes the transcription of Fcgr1, which was involved in activating microglia pyroptosis.
3
Knocking down Cebpb or Fcgr1, or the pyroptosis inhibitor VX765 inhibited neuronal apoptosis and improved neurological recovery in mice.

Research Summary

This study demonstrates a significant upregulation of C/EBPβ in microglia in a mouse model of SCI, suggesting its involvement in the post-SCI neuroinflammatory response. The research uncovers that C/EBPβ activates microglial Fcgr1 transcription, and this C/EBPβ-Fcgr1 axis participates in neuroinflammation by activating microglia pyroptosis. Inhibition of the C/EBPβ-Fcgr1 axis, either through the administration of the pyroptosis inhibitor VX765 or by knocking down Cebpb or Fcgr1, effectively inhibited microglia pyroptosis, suppressed pro-inflammatory cytokine secretion, and promoted neurological repair post-SCI.

Practical Implications

Therapeutic Target Identification

The C/EBPβ-Fcgr1 axis can be a therapeutic strategy to alleviate the microglial neuroinflammatory response and promote the neurological repair post-SCI.

Drug Development

Development of novel drugs targeting C/EBPβ or its downstream targets like Fcgr1 for SCI treatment.

Personalized Medicine

Identification of patients who may benefit most from therapies targeting the C/EBPβ-Fcgr1 axis.

Study Limitations

1
In vivo knockdown assays did not specifically target microglia.
2
The study acknowledges the need for further validation using Cre-loxp system to knock down Cebpb specifically in microglia.
3
No datasets were generated or analysed during the current study.

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