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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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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338923/
https://www.ncbi.nlm.nih.gov/pubmed/34349124
http://dx.doi.org/10.1038/s41467-021-25065-w
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author 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
author_facet 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
author_sort Sobecki, Michal
collection PubMed
description 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.
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spelling pubmed-83389232021-08-12 NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence 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 Nat Commun Article 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. Nature Publishing Group UK 2021-08-04 /pmc/articles/PMC8338923/ /pubmed/34349124 http://dx.doi.org/10.1038/s41467-021-25065-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence
title NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence
title_full NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence
title_fullStr NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence
title_full_unstemmed NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence
title_short NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence
title_sort nk cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338923/
https://www.ncbi.nlm.nih.gov/pubmed/34349124
http://dx.doi.org/10.1038/s41467-021-25065-w
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