Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated with Interface Dermatitis
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Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated with Interface Dermatitis. / Lauffer, Felix; Jargosch, Manja; Krause, Linda; Garzorz-Stark, Natalie; Franz, Regina; Roenneberg, Sophie; Böhner, Alexander; Mueller, Nikola S; Theis, Fabian J; Schmidt-Weber, Carsten B; Biedermann, Tilo; Eyerich, Stefanie; Eyerich, Kilian.
in: J INVEST DERMATOL, Jahrgang 138, Nr. 8, 08.2018, S. 1785-1794.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated with Interface Dermatitis
AU - Lauffer, Felix
AU - Jargosch, Manja
AU - Krause, Linda
AU - Garzorz-Stark, Natalie
AU - Franz, Regina
AU - Roenneberg, Sophie
AU - Böhner, Alexander
AU - Mueller, Nikola S
AU - Theis, Fabian J
AU - Schmidt-Weber, Carsten B
AU - Biedermann, Tilo
AU - Eyerich, Stefanie
AU - Eyerich, Kilian
N1 - Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2018/8
Y1 - 2018/8
N2 - Interface dermatitis is a characteristic histological pattern that occurs in autoimmune and chronic inflammatory skin diseases. It is unknown whether a common mechanism orchestrates this distinct type of skin inflammation. Here we investigated the overlap of two different interface dermatitis positive skin diseases, lichen planus and lupus erythematosus. The shared transcriptome signature pointed toward a strong type I immune response, and biopsy-derived T cells were dominated by IFN-γ and tumor necrosis factor alpha (TNF-α) positive cells. The transcriptome of keratinocytes stimulated with IFN-γ and TNF-α correlated significantly with the shared gene regulations of lichen planus and lupus erythematosus. IFN-γ, TNF-α, or mixed supernatant of lesional T cells induced signs of keratinocyte cell death in three-dimensional skin equivalents. We detected a significantly enhanced epidermal expression of receptor-interacting-protein-kinase 3, a key regulator of necroptosis, in interface dermatitis. Phosphorylation of receptor-interacting-protein-kinase 3 and mixed lineage kinase domain like pseudokinase was induced in keratinocytes on stimulation with T-cell supernatant-an effect that was dependent on the presence of either IFN-γ or TNF-α in the T-cell supernatant. Small hairpin RNA knockdown of receptor-interacting-protein-kinase 3 prevented cell death of keratinocytes on stimulation with IFN-γ or TNF-α. In conclusion, type I immunity is associated with lichen planus and lupus erythematosus and induces keratinocyte necroptosis. These two mechanisms are potentially involved in interface dermatitis.
AB - Interface dermatitis is a characteristic histological pattern that occurs in autoimmune and chronic inflammatory skin diseases. It is unknown whether a common mechanism orchestrates this distinct type of skin inflammation. Here we investigated the overlap of two different interface dermatitis positive skin diseases, lichen planus and lupus erythematosus. The shared transcriptome signature pointed toward a strong type I immune response, and biopsy-derived T cells were dominated by IFN-γ and tumor necrosis factor alpha (TNF-α) positive cells. The transcriptome of keratinocytes stimulated with IFN-γ and TNF-α correlated significantly with the shared gene regulations of lichen planus and lupus erythematosus. IFN-γ, TNF-α, or mixed supernatant of lesional T cells induced signs of keratinocyte cell death in three-dimensional skin equivalents. We detected a significantly enhanced epidermal expression of receptor-interacting-protein-kinase 3, a key regulator of necroptosis, in interface dermatitis. Phosphorylation of receptor-interacting-protein-kinase 3 and mixed lineage kinase domain like pseudokinase was induced in keratinocytes on stimulation with T-cell supernatant-an effect that was dependent on the presence of either IFN-γ or TNF-α in the T-cell supernatant. Small hairpin RNA knockdown of receptor-interacting-protein-kinase 3 prevented cell death of keratinocytes on stimulation with IFN-γ or TNF-α. In conclusion, type I immunity is associated with lichen planus and lupus erythematosus and induces keratinocyte necroptosis. These two mechanisms are potentially involved in interface dermatitis.
KW - Journal Article
U2 - 10.1016/j.jid.2018.02.034
DO - 10.1016/j.jid.2018.02.034
M3 - SCORING: Journal article
C2 - 29526761
VL - 138
SP - 1785
EP - 1794
JO - J INVEST DERMATOL
JF - J INVEST DERMATOL
SN - 0022-202X
IS - 8
ER -
