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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 inflammatory genes in lichen planus.

J. Invest. Dermatol., DOI: 10.1016/j.jid.2024.11.017 (2024)
DOI PMC
: Postprint online verfügbar 01/2026
Lichen planus (LP) is a chronic inflammatory disease (ISD) affecting skin, mucosa, nail, and hair. Previous studies demonstrated a pivotal role of type 1 immunity in LP, as 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 seq of skin biopsies revealed a high expression of DAPK1 in LP compared to psoriasis and atopic dermatitis (AD). DAPK1 expression in human keratinocytes was induced by IFN-γ, TNF and IL-32. CRISPR/Cas9 mediated DAPK1 knock-out (KO) led to a decreased rate of cell death and induction of pro-apoptotic proteins (BAX, cPARP) in human keratinocytes upon stimulation with the supernatant T cells derived from LP skin biopsies (LP-TCS). Meanwhile, DAPK1 KO 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-TCS. 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 towards previously unreported therapeutic approaches for activating or stabilizing DAPK1 in LP.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Apoptosis ; Death Associated Protein Kinase 1 ; Interface Dermatitis ; Lichen Planus ; Necroptosis
ISSN (print) / ISBN 0022-202X
e-ISSN 1523-1747
Zeitschrift Journal of Investigative Dermatology, The
Verlag Elsevier
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Allergy Research (IAF)
Institute of Computational Biology (ICB)