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

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 d...

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Veröffentlicht in:Nature communications 2021-08, Vol.12 (1), p.4700-4700, Article 4700
Hauptverfasser: Sobecki, Michal, Krzywinska, Ewelina, Nagarajan, Shunmugam, Audigé, Annette, Huỳnh, Khanh, Zacharjasz, Julian, Debbache, Julien, Kerdiles, Yann, Gotthardt, Dagmar, Takeda, Norihiko, Fandrey, Joachim, Sommer, Lukas, Sexl, Veronika, Stockmann, Christian
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Sprache:eng
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Zusammenfassung: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. During wound healing and infection in the skin there is a hypoxic environment involving HIF-1α and NK cells. Here the authors show that NK cells through HIF-1α provide a cross-regulatory balance to provide an adequate antimicrobial defence that can inhibit subsequent wound healing.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-25065-w