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NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence

Author

Listed:
  • Michal Sobecki

    (University of Zurich, Institute of Anatomy)

  • Ewelina Krzywinska

    (University of Zurich, Institute of Anatomy)

  • Shunmugam Nagarajan

    (University of Zurich, Institute of Anatomy)

  • Annette Audigé

    (University of Zurich, Institute of Anatomy)

  • Khanh Huỳnh

    (University of Zurich, Institute of Anatomy)

  • Julian Zacharjasz

    (University of Zurich, Institute of Anatomy)

  • Julien Debbache

    (University of Zurich, Institute of Anatomy)

  • Yann Kerdiles

    (Centre d’Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280)

  • Dagmar Gotthardt

    (University of Veterinary Medicine)

  • Norihiko Takeda

    (Jichi Medical University, 3311-1 Yakushiji)

  • Joachim Fandrey

    (Universitätsklinikum Essen, Universität Duisburg-Essen)

  • Lukas Sommer

    (University of Zurich, Institute of Anatomy)

  • Veronika Sexl

    (University of Veterinary Medicine)

  • Christian Stockmann

    (University of Zurich, Institute of Anatomy
    Comprehensive Cancer Center Zurich)

Abstract

During skin injury, immune response and repair mechanisms have to be coordinated for rapid skin regeneration and the prevention of microbial infections. Natural Killer (NK) cells infiltrate hypoxic skin lesions and Hypoxia-inducible transcription factors (HIFs) mediate adaptation to low oxygen. We demonstrate that mice lacking the Hypoxia-inducible factor (HIF)-1α isoform in NK cells show impaired release of the cytokines Interferon (IFN)-γ and Granulocyte Macrophage - Colony Stimulating Factor (GM-CSF) as part of a blunted immune response. This accelerates skin angiogenesis and wound healing. Despite rapid wound closure, bactericidal activity and the ability to restrict systemic bacterial infection are impaired. Conversely, forced activation of the HIF pathway supports cytokine release and NK cell-mediated antibacterial defence including direct killing of bacteria by NK cells despite delayed wound closure. Our results identify, HIF-1α in NK cells as a nexus that balances antimicrobial defence versus global repair in the skin.

Suggested Citation

  • Michal Sobecki & Ewelina Krzywinska & Shunmugam Nagarajan & Annette Audigé & Khanh Huỳnh & Julian Zacharjasz & Julien Debbache & Yann Kerdiles & Dagmar Gotthardt & Norihiko Takeda & Joachim Fandrey & , 2021. "NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25065-w
    DOI: 10.1038/s41467-021-25065-w
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    Cited by:

    1. Ying Zhang & Shenqiang Wang & Yinxian Yang & Sheng Zhao & Jiahuan You & Junxia Wang & Jingwei Cai & Hao Wang & Jie Wang & Wei Zhang & Jicheng Yu & Chunmao Han & Yuqi Zhang & Zhen Gu, 2023. "Scarless wound healing programmed by core-shell microneedles," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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