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Kurzen, N.* ; Mubarak, M.* ; Eigemann, J. ; Seiringer, P.* ; Wasserer, S.* ; Hillig, C. ; Menden, M.P. ; Biedermann, T.* ; Schmidt-Weber, C.B. ; Eyerich, K.* ; Jargosch, M. ; Eyerich, S. ; Lauffer, F.*

Death-associated protein kinase 1 dampens keratinocyte necroptosis and expression of genes in lichen planus.

J. Invest. Dermatol. 145, 1921-1929.e13 (2025)
Verlagsversion Forschungsdaten DOI
Open Access Hybrid
Creative Commons Lizenzvertrag
Lichen planus (LP) is a chronic inflammatory disease affecting the skin, mucosa, nail, and hair. Previous studies demonstrated a pivotal role of type 1 immunity in LP because infiltrating T cells trigger apoptosis and necroptosis in the epidermis. In this study, we investigated the role of DAPK1 in LP with special focus on its role in mediating cell death and inflammation. Bulk RNA sequencing of skin biopsies revealed a high expression of DAPK1 in LP compared with that in psoriasis and atopic dermatitis. DAPK1 expression in human keratinocytes was induced by IFN-g, TNF, and IL-32. CRISPR/Cas9-mediated DAPK1 knockout led to a decreased rate of cell death and induction of proapoptotic proteins (BAX, cPARP) in human keratinocytes upon stimulation with the supernatant T cells derived from LP skin biopsies. Meanwhile, DAPK1 knockout resulted in an induction of kinases involved in necroptosis (RIPK3) and an upregulation of inflammatory genes (CXCL9, CXCL10, CXCL11, IL32, CCL2) after stimulation with LP supernatant T cells. In summary, we demonstrate that DAPK1 mediates keratinocyte apoptosis under type 1 inflammatory conditions and thereby counteracts necroptosis and regulation of inflammatory genes. These findings point toward previously unreported therapeutic approaches for activating or stabilizing DAPK1 in LP.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Apoptosis; Death-associated protein kinase 1; Interface dermatitis; Lichen planus; Necroptosis; Induced Lung Injury; Atopic-dermatitis; Immune-response; Inflammation; Apoptosis; Autophagy; Cells
ISSN (print) / ISBN 0022-202X
e-ISSN 1523-1747
Zeitschrift Journal of Investigative Dermatology, The
Quellenangaben Band: 145, Heft: 8, Seiten: 1921-1929.e13 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Allergy Research (IAF)
Institute of Computational Biology (ICB)
Förderungen Doctoral Program Translational Medicine of the School of Medicine and Health of the Technical University of Munich