Journal articles
NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence
Michal Sobecki
1
Ewelina Krzywinska
1
Shunmugam Nagarajan
1
Annette Audigé
1
Khanh Huỳnh
1
Julian Zacharjasz
1
Julien Debbache
1
Yann Kerdiles
2
Dagmar Gotthardt
3
Norihiko Takeda
4
Joachim Fandrey
5
Lukas Sommer
1
Veronika Sexl
3
Christian Stockmann
1
Michal Sobecki 1
Author ORCID : https://orcid.org/0000-0002-8177-0327
Ewelina Krzywinska 1
Author ORCID : https://orcid.org/0000-0002-4311-2972
Shunmugam Nagarajan 1
Author
Annette Audigé 1
Author
Khanh Huỳnh 1
Author
Julian Zacharjasz 1
Author ORCID : https://orcid.org/0000-0003-2091-7070
Julien Debbache 1
Author
Yann Kerdiles 2
Author ORCID : https://orcid.org/0000-0002-8605-1073
Dagmar Gotthardt 3
Author ORCID : https://orcid.org/0000-0002-8416-1236
Norihiko Takeda 4
Author
Joachim Fandrey 5
Author ORCID : https://orcid.org/0000-0001-9585-0531
Lukas Sommer 1
Author ORCID : https://orcid.org/0000-0002-1143-7908
Veronika Sexl 3
Author
Christian Stockmann 1
Author ORCID : https://orcid.org/0000-0002-9726-6838
1
Université de Zurich (Switzerland)
- UZH - Universität Zürich [Zürich] = University of Zurich (Rämistrasse 71 CH-8006 Zürich - Switzerland)
2
CIML - Centre d'Immunologie de Marseille - Luminy (Parc scientifique et technologique de Luminy - 163, avenue de Luminy - Case 906 - 13288 Marseille cedex 09 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : UMR_S 1104 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7280 (France)
- AMU - Aix Marseille Université : UM 2 (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
3
Université médicale de Vienne, Autriche (France)
4
Jichi Medical University (3311-1 Yakushiji - Shimotsuke-shi - Tochigi, 329-0498 - Japan)
5
Uniklinik Essen - Universitätsklinikum Essen [Universität Duisburg-Essen] (Hufelandstraße 55, 45147 Essen - Germany)
Abstract : 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.
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Journal articles
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https://hal-amu.archives-ouvertes.fr/hal-03374633
Contributor : Anita Dumenil Connect in order to contact the contributor
Submitted on : Tuesday, October 12, 2021 - 11:29:28 AM
Last modification on : Thursday, January 6, 2022 - 3:46:55 AM
Contributor : Anita Dumenil Connect in order to contact the contributor
Submitted on : Tuesday, October 12, 2021 - 11:29:28 AM
Last modification on : Thursday, January 6, 2022 - 3:46:55 AM
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- HAL Id : hal-03374633, version 1
- DOI : 10.1038/s41467-021-25065-w
Citation
Michal Sobecki, Ewelina Krzywinska, Shunmugam Nagarajan, Annette Audigé, Khanh Huỳnh, et al.. NK cells in hypoxic skin mediate a trade-off between wound healing and antibacterial defence. Nature Communications, Nature Publishing Group, 2021, 12 (1), ⟨10.1038/s41467-021-25065-w⟩. ⟨hal-03374633⟩
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