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Cited by 275Spinal Cord Injury ResearchNeuroinflammation and Neurodegeneration MechanismsNerve injury and regeneration

Microglia and macrophages promote corralling, wound compaction and recovery after spinal cord injury via Plexin-B2

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Zhou, Xiang, Wahane, Shalaka, Friedl, Marie-Sophie, Kluge, Michael, Friedel, Caroline C., Avrampou, Kleopatra, Zachariou, Venetia, Guo, Lei +4 more·2020·Nature Neuroscience
DOI 10.1038/s41593-020-0597-7PMC PMC7412870
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Abstract

Tissue repair after spinal cord injury requires the mobilization of immune and glial cells to form a protective barrier that seals the wound and facilitates debris clearing, inflammatory containment and matrix compaction. This process involves corralling, wherein phagocytic immune cells become confined to the necrotic core, which is surrounded by an astrocytic border. Here we elucidate a temporally distinct gene signature in injury-activated microglia and macrophages (IAMs) that engages axon guidance pathways. Plexin-B2 is upregulated in IAMs and is required for motor sensory recovery after spinal cord injury. Plexin-B2 deletion in myeloid cells impairs corralling, leading to diffuse tissue damage, inflammatory spillover and hampered axon regeneration. Corralling begins early and requires Plexin-B2 in both microglia and macrophages. Mechanistically, Plexin-B2 promotes microglia motility, steers IAMs away from colliding cells and facilitates matrix compaction. Our data therefore establish Plexin-B2 as an important link that integrates biochemical cues and physical interactions of IAMs with the injury microenvironment during wound healing.

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References 67 · Cited by 275

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Authors
Zhou, X., Wahane, S., Friedl, M.-S., Kluge, M., Friedel, C. C., Avrampou, K., Zachariou, V., Guo, L., Zhang, B., He, X., Friedel, R. H., & Zou, H.
Affiliations
  • Second Affiliated Hospital of Xi'an Jiaotong University (CN)
  • Icahn School of Medicine at Mount Sinai (US)
  • Ludwig-Maximilians-Universität München (DE)
Corresponding author
  • Friedel, Roland H.
  • Zou, Hongyan
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2020-02-28
Volume
23
Issue
3
Pages
337-350
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/s41593-020-0597-7
PMC
PMC7412870
OpenAlex
W3008198525
Cited by
275
References
67
Citations by year
2026: 28 · 2025: 51 · 2024: 51 · 2023: 41 · 2022: 50 · 2021: 39 · 2020: 15
FWCI
23.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • New York State Department of Health (DOH01-C32634GG, DOH01-C33268GG)
  • Deutsche Forschungsgemeinschaft (FR2938/7-1, CRC 1123 (Z2))
  • U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NS086444, NS093537, NS092735), NS073596)
  • U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (DAO8227)
  • Craig H. Neilsen Foundation (#476516)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Keywords
spinal cord injury, microglia, macrophages, Plexin-B2, axon guidance, axon regeneration, sensorimotor recovery, tissue repair
MeSH terms
Animals, Axons, Locomotion, Macrophages, Nerve Regeneration, Nerve Tissue Proteins, Neural Pathways, Phagocytosis, Sensation, Spinal Cord Injuries, Wound Healing, Microglia, Recovery of Function, Mice, Cellular Microenvironment

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