ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1617737
This article is part of the Research TopicAdvances in Skin Barrier Dysfunction and Disease PathogenesisView all articles
Epiplakin expression is lost in psoriatic skin lesions and is downregulated by IFN-γ in ex vivo skin cultures
Provisionally accepted
Hannes Kühtreiber1
Corinne Drexler2,3Melanie Salek1Lisa Auer4
Johannes Griss1
Michael Mildner1*
Peter Fuchs2,3*- 1Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria
- 2Max Perutz Labs,Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria
- 3University of Vienna, Max Perutz Labs, Department of Biochemistry and Cell Biology, Dr.-Bohr-Gasse 9, 1030, Vienna, Austria
- 4Department of Thoracic Surgery, Applied Immunology Laboratory, Medical University of Vienna, 1090, Vienna, Austria
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Proteins of the plakin family are predominantly expressed in the epidermis and play a crucial role in cytoskeletal assembly by crosslinking intracellular structural components with cell–cell junctions and the plasma membrane. While most plakins are critical for maintaining epidermal integrity, the role of epiplakin (EPPK1) in inflammatory skin disorders has not been thoroughly investigated. We therefore used single‑cell RNA sequencing (scRNAseq) analysis, immunofluorescence, and ex vivo cytokine treatment of human skin explants to investigate EPPK1 regulation in psoriasis. ScRNAseq analysis of psoriatic and healthy skin revealed that EPPK1 was the only member of the plakin family showing specific downregulation in the epidermis of psoriatic lesions. This finding was corroborated at the protein level by immunostaining of human psoriasis samples showing a specific downregulation of EPPK1 in the suprabasal granular layer of psoriatic epidermis. Transcriptomic profiling of Eppk1⁻/⁻ murine epidermis revealed reduced expression of genes involved in epithelial adhesion and lipid metabolism, partially overlapping with the psoriatic keratinocyte signature, suggesting that EPPK1 loss may predispose the skin to barrier dysfunction under inflammatory stress. Investigation of the mechanism underlying the EPPK1 regulation in psoriasis revealed that interferon‑γ (IFN‑γ) was the main cytokine involved in its downregulation in human ex vivo skin. Collectively, our findings demonstrate a specific IFN-γ-dependent downregulation of EPPK1 in psoriasis, suggesting that lack of EPPK1 might contribute to the epithelial defects observed in this inflammatory skin condition.
Keywords: Plakins, Epiplakin, Psoriasis, atopic dermatitis, scRNAseq
Received: 24 Apr 2025; Accepted: 29 Jun 2025.
Copyright: © 2025 Kühtreiber, Drexler, Salek, Auer, Griss, Mildner and Fuchs. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Michael Mildner, Department of Dermatology, Medical University of Vienna, 1090, Vienna, Austria
Peter Fuchs, Max Perutz Labs,Vienna Biocenter Campus (VBC), Dr.-Bohr-Gasse 9, 1030, Vienna, Austria
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.