PUBLICATION

Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration

Authors
Tsarouchas, T.M., Wehner, D., Cavone, L., Munir, T., Keatinge, M., Lambertus, M., Underhill, A., Barrett, T., Kassapis, E., Ogryzko, N., Feng, Y., van Ham, T.J., Becker, T., Becker, C.G.
ID
ZDB-PUB-181109-2
Date
2018
Source
Nature communications   9: 4670 (Journal)
Registered Authors
Becker, Catherina G., Becker, Thomas, Feng, Yi, Keatinge, Marcus, Ogryzko, Nikolay, Tsarouchas, Themistoklis, van Ham, Tjakko, Wehner, Daniel
Keywords
none
MeSH Terms
  • Animals
  • Axons/metabolism
  • Collagen Type XII/metabolism
  • Inflammation Mediators/metabolism*
  • Interleukin-1beta/metabolism*
  • Macrophages/metabolism*
  • Microglia/metabolism
  • Microglia/pathology
  • Mutation/genetics
  • Nerve Regeneration*
  • Neutrophils/metabolism
  • Spinal Cord/metabolism*
  • Spinal Cord/pathology
  • Tumor Necrosis Factor-alpha/metabolism*
  • Zebrafish/immunology
  • Zebrafish/metabolism*
PubMed
30405119 Full text @ Nat. Commun.
Abstract
Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also in successfully regenerating zebrafish. However, the role of the immune response in successful regeneration is poorly defined. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in spinal-lesioned zebrafish larvae. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary for repair. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Tnf-α and Il-1β. Inhibiting Tnf-α does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-α. In contrast, decreasing Il-1β levels or number of Il-1β+ neutrophils rescue functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1β function impairs regeneration in irf8 and wildtype animals. Hence, inflammation is dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish.
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Errata and Notes