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

Author

Listed:
  • Themistoklis M. Tsarouchas

    (University of Edinburgh)

  • Daniel Wehner

    (University of Edinburgh
    Technische Universität Dresden, DFG-Center of Regenerative Therapies Dresden)

  • Leonardo Cavone

    (University of Edinburgh)

  • Tahimina Munir

    (University of Edinburgh)

  • Marcus Keatinge

    (University of Edinburgh)

  • Marvin Lambertus

    (University of Edinburgh
    University of Oslo)

  • Anna Underhill

    (University of Edinburgh)

  • Thomas Barrett

    (University of Edinburgh)

  • Elias Kassapis

    (University of Edinburgh)

  • Nikolay Ogryzko

    (Queen’s Medical Research Institute, University of Edinburgh)

  • Yi Feng

    (Queen’s Medical Research Institute, University of Edinburgh)

  • Tjakko J. Ham

    (Erasmus University Medical Center)

  • Thomas Becker

    (University of Edinburgh)

  • Catherina G. Becker

    (University of Edinburgh)

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.

Suggested Citation

  • Themistoklis M. Tsarouchas & Daniel Wehner & Leonardo Cavone & Tahimina Munir & Marcus Keatinge & Marvin Lambertus & Anna Underhill & Thomas Barrett & Elias Kassapis & Nikolay Ogryzko & Yi Feng & Tjak, 2018. "Dynamic control of proinflammatory cytokines Il-1β and Tnf-α by macrophages in zebrafish spinal cord regeneration," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07036-w
    DOI: 10.1038/s41467-018-07036-w
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    Cited by:

    1. Julia Kolb & Vasiliki Tsata & Nora John & Kyoohyun Kim & Conrad Möckel & Gonzalo Rosso & Veronika Kurbel & Asha Parmar & Gargi Sharma & Kristina Karandasheva & Shada Abuhattum & Olga Lyraki & Timon Be, 2023. "Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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