Apremilast prevents blistering in human epidermis and stabilizes keratinocyte adhesion in pemphigus

Anna M. Sigmund, Markus Winkler, Sophia Engelmayer, Daniela Kugelmann, Desalegn T. Egu, Letyfee S. Steinert, Michael Fuchs, Matthias Hiermaier, Mariya Y. Radeva, Franziska C. Bayerbach, Elisabeth Butz, Stefan Kotschi, Christoph Hudemann, Michael Hertl, Sunil Yeruva, Enno Schmidt, Amir S. Yazdi, Kamran Ghoreschi, Franziska Vielmuth () and Jens Waschke ()
Additional contact information
Anna M. Sigmund: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Markus Winkler: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Sophia Engelmayer: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Daniela Kugelmann: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Desalegn T. Egu: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Letyfee S. Steinert: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Michael Fuchs: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Matthias Hiermaier: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Mariya Y. Radeva: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Franziska C. Bayerbach: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Elisabeth Butz: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Stefan Kotschi: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Christoph Hudemann: Philipps-University Marburg
Michael Hertl: Philipps-University Marburg
Sunil Yeruva: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Enno Schmidt: University of Lübeck
Amir S. Yazdi: Rheinisch-Westfälische Technische Hochschule Aachen (RWTH) Aachen University
Kamran Ghoreschi: Venereology and Allergology, Charité-Universitätsmedizin Berlin
Franziska Vielmuth: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich
Jens Waschke: Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Pemphigus vulgaris is a life-threatening blistering skin disease caused by autoantibodies destabilizing desmosomal adhesion. Current therapies focus on suppression of autoantibody formation and thus treatments directly stabilizing keratinocyte adhesion would fulfill an unmet medical need. We here demonstrate that apremilast, a phosphodiesterase 4 inhibitor used in psoriasis, prevents skin blistering in pemphigus vulgaris. Apremilast abrogates pemphigus autoantibody-induced loss of keratinocyte cohesion in ex-vivo human epidermis, cultured keratinocytes in vitro and in vivo in mice. In parallel, apremilast inhibits keratin retraction as well as desmosome splitting, induces phosphorylation of plakoglobin at serine 665 and desmoplakin assembly into desmosomal plaques. We established a plakoglobin phospho-deficient mouse model that reveals fragile epidermis with altered organization of keratin filaments and desmosomal cadherins. In keratinocytes derived from these mice, intercellular adhesion is impaired and not rescued by apremilast. These data identify an unreported mechanism of desmosome regulation and propose that apremilast stabilizes keratinocyte adhesion and is protective in pemphigus.

Date: 2023
References: View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-35741-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35741-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-35741-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().