Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated with Interface Dermatitis
Lauffer F, Jargosch M, Krause L, Garzorz-Stark N, Franz R, Roenneberg S, Boehner A, Mueller NS, Theis FJ, Schmidt-Weber CB, Biedermann T, Eyerich S, Eyerich K (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 138
Pages Range: 1785-1794
Journal Issue: 8
DOI: 10.1016/j.jid.2018.02.034
Abstract
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.
Involved external institutions
Technische Universität München (TUM)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Technische Universität Dresden
Germany (DE)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Technische Universität Dresden
Germany (DE)
How to cite
APA:
Lauffer, F., Jargosch, M., Krause, L., Garzorz-Stark, N., Franz, R., Roenneberg, S.,... Eyerich, K. (2018). Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated with Interface Dermatitis. Journal of Investigative Dermatology, 138(8), 1785-1794. https://doi.org/10.1016/j.jid.2018.02.034
MLA:
Lauffer, Felix, et al. "Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated with Interface Dermatitis." Journal of Investigative Dermatology 138.8 (2018): 1785-1794.
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