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Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated with Interface Dermatitis.
J Invest Dermatol. 2018 08; 138(8):1785-1794.JI

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.

Authors+Show Affiliations

Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany. Electronic address: felix.lauffer@tum.de.Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.Institute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany.Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.Institute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany.Institute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany; Department of Mathematics, Technical University of Munich, Garching, Germany.ZAUM-Center of Allergy and Environment, Technical University and Helmholtz Center Munich, Munich, Germany.Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.ZAUM-Center of Allergy and Environment, Technical University and Helmholtz Center Munich, Munich, Germany.Department of Dermatology and Allergy, Technical University of Munich, Munich, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29526761

Citation

Lauffer, Felix, et al. "Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated With Interface Dermatitis." The Journal of Investigative Dermatology, vol. 138, no. 8, 2018, pp. 1785-1794.
Lauffer F, Jargosch M, Krause L, et al. Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated with Interface Dermatitis. J Invest Dermatol. 2018;138(8):1785-1794.
Lauffer, F., Jargosch, M., Krause, L., Garzorz-Stark, N., Franz, R., Roenneberg, S., Böhner, A., Mueller, N. S., Theis, F. J., Schmidt-Weber, C. B., Biedermann, T., Eyerich, S., & Eyerich, K. (2018). Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated with Interface Dermatitis. The Journal of Investigative Dermatology, 138(8), 1785-1794. https://doi.org/10.1016/j.jid.2018.02.034
Lauffer F, et al. Type I Immune Response Induces Keratinocyte Necroptosis and Is Associated With Interface Dermatitis. J Invest Dermatol. 2018;138(8):1785-1794. PubMed PMID: 29526761.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2018/03/09/ PY - 2017/08/22/received PY - 2018/02/23/revised PY - 2018/02/26/accepted PY - 2018/3/13/pubmed PY - 2019/6/14/medline PY - 2018/3/13/entrez SP - 1785 EP - 1794 JF - The Journal of investigative dermatology JO - J. Invest. Dermatol. VL - 138 IS - 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. SN - 1523-1747 UR - https://www.unboundmedicine.com/medline/citation/29526761/Type_I_Immune_Response_Induces_Keratinocyte_Necroptosis_and_Is_Associated_with_Interface_Dermatitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-202X(18)30215-X DB - PRIME DP - Unbound Medicine ER -