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IL-17 signaling in keratinocytes orchestrates the defense against Staphylococcus aureus skin infection

Keratinocytes (KCs) form the outer epithelial barrier of the body, protecting against invading pathogens. Mice lacking the IL-17RA or both IL-17A and IL-17F develop spontaneous Staphylococcus aureus skin infections. We found a marked expansion of T17 cells, comprised of RORγt-expressing γδ T cells a...

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Main Authors: Moos, Sonja (Author) , Regen, Tommy (Author) , Wanke, Florian (Author) , Tian, Yizhu (Author) , Arendholz, Lucas T. (Author) , Hauptmann, Judith (Author) , Heinen, André P. (Author) , Bleul, Lisa (Author) , Bier, Katharina (Author) , El Malki, Khalifa (Author) , Reinhardt, Christoph (Author) , Prinz, Immo (Author) , Diefenbach, Andreas (Author) , Wolz, Christiane (Author) , Schittek, Birgit (Author) , Waisman, Ari (Author) , Kurschus, Florian (Author)
Format: Article (Journal)
Language:English
Published: July 2023
In: The journal of investigative dermatology
Year: 2023, Volume: 143, Issue: 7, Pages: 1257-1267.e10
ISSN:1523-1747
DOI:10.1016/j.jid.2023.01.016
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jid.2023.01.016
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022202X23000702
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Author Notes:Sonja Moos, Tommy Regen, Florian Wanke, Yizhu Tian, Lucas T. Arendholz, Judith Hauptmann, André P. Heinen, Lisa Bleul, Katharina Bier, Khalifa El Malki, Christoph Reinhardt, Immo Prinz, Andreas Diefenbach, Christiane Wolz, Birgit Schittek, Ari Waisman and Florian C. Kurschus
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Summary:Keratinocytes (KCs) form the outer epithelial barrier of the body, protecting against invading pathogens. Mice lacking the IL-17RA or both IL-17A and IL-17F develop spontaneous Staphylococcus aureus skin infections. We found a marked expansion of T17 cells, comprised of RORγt-expressing γδ T cells and T helper 17 cells in the skin-draining lymph nodes of these mice. Contradictory to previous suggestions, this expansion was not a result of a direct negative feedback loop because we found no expansion of T17 cells in mice lacking IL-17 signaling specifically in T cells. Instead, we found that the T17 expansion depended on the microbiota and was observed only when KCs were deficient for IL-17RA signaling. Indeed, mice that lack IL-17RA only in KCs showed an increased susceptibility to experimental epicutaneous infection with S. aureus together with an accumulation of IL-17A−producing γδ T cells. We conclude that deficiency of IL-17RA on KCs leads to microbiota dysbiosis in the skin, which triggers the expansion of IL-17A−producing T cells. Our data show that KCs are the primary target cells of IL-17A and IL-17F, coordinating the defense against microbial invaders in the skin.
Item Description:Online verfügbar: 2. Februar 2023, Artikelversion: 21. Juni 2023
Gesehen am 23.08.2023
Physical Description:Online Resource
ISSN:1523-1747
DOI:10.1016/j.jid.2023.01.016

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