Buchumschlag

IFNγ causes keratinocyte necroptosis in acute graft-versus-host disease

Epidermal keratinocytes form the first-line cellular barrier of the skin for protection against external injuries and maintenance of local tissue homeostasis. Expression of ZBP1 was shown to cause necroptotic keratinocyte cell death and skin inflammation in mice. We sought to characterize the releva...

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Hauptverfasser: Freund, Lukas (VerfasserIn) , Oehrl, Stephanie (VerfasserIn) , Schwingen, Julius (VerfasserIn) , Häberle, Stefanie (VerfasserIn) , Döbel, Thomas (VerfasserIn) , Lee, Paul D. H. (VerfasserIn) , Meisel, Stefan (VerfasserIn) , Mihalceanu, Silvia (VerfasserIn) , Rußwurm, Martin (VerfasserIn) , Luft, Thomas (VerfasserIn) , Schäkel, Knut (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 21 August 2023
In: The journal of investigative dermatology
Year: 2023, Jahrgang: 143, Heft: 9, Pages: 1746-1756, e1-e9
ISSN:1523-1747
DOI:10.1016/j.jid.2023.02.025
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jid.2023.02.025
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022202X23001744
Volltext
Verfasserangaben:Lukas Freund, Stephanie Oehrl, Julius Schwingen, Stefanie Haeberle, Thomas Döbel, Paul D.H. Lee, Stefan Meisel, Silvia Mihalceanu, Martin Rußwurm, Thomas Luft and Knut Schäkel
Beschreibung
Zusammenfassung:Epidermal keratinocytes form the first-line cellular barrier of the skin for protection against external injuries and maintenance of local tissue homeostasis. Expression of ZBP1 was shown to cause necroptotic keratinocyte cell death and skin inflammation in mice. We sought to characterize the relevance of ZBP1 and necroptosis in human keratinocytes and type 1−driven cutaneous acute graft-versus-host disease. in this study, we identify ZBP1 expression, necroptosis, and interface dermatitis as being the hallmarks of acute graft-versus-host disease. ZBP1 expression was dependent on leukocyte-derived IFNγ, and interference with IFNγ signaling by Jak inhibition prevented cell death. In predominantly IL-17−driven psoriasis, both ZBP1 expression and necroptosis could not be detected. Of note, in contrast to the signaling in mice, ZBP1 signaling in human keratinocytes was not affected by RIPK1’s presence. These findings show that ZBP1 drives inflammation in IFNγ-dominant type 1 immune responses in human skin and may further point to a general role of ZBP1-mediated necroptosis.
Beschreibung:Online verfügbar 6 March 2023, Version des Artikels 21 August 2023
Gesehen am 13.10.2023
Beschreibung:Online Resource
ISSN:1523-1747
DOI:10.1016/j.jid.2023.02.025

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