The human skin organ culture model as an optimal complementary tool for murine pemphigus models

Veronika Hartmann, William V.J. Hariton, Siavash Rahimi, Christoph M. Hammers, Ralf J. Ludwig, Eliane J. Müller, Jennifer E. Hundt*

*Korrespondierende/r Autor/-in für diese Arbeit
2 Zitate (Scopus)

Abstract

Pemphigus is a severe autoimmune bullous disease of the skin and/or mucous membranes caused by autoantibodies that mainly target the adhesion proteins desmoglein (Dsg) 3 and/or Dsg1. Clinically, pemphigus is characterized by flaccid blistering, leading to severe water and electrolyte loss. Before the introduction of corticosteroid treatment, the disease turned out to be fatal in many cases. Despite recent therapeutic improvements, treatment of pemphigus patients is centred on prolonged systemic immunosuppression and remains challenging. Current drug development for pemphigus has a strong focus on disease-causing B cells and autoantibodies and, more recently, also on modulating autoantibody-induced tissue pathology and keratinocyte signalling. This drug development requires reliable pre-clinical model systems replicating the pathogenesis of the human disease. Among those are neonatal and adult mouse models based on the transfer of Dsg3, Dsg1/3 or Dsg1-specific autoantibodies. To reduce the number of animal experiments, we recently established a standardized human skin organ culture (HSOC) model for pemphigus. This model reproduces the clinical phenotype of autoantibody-induced tissue pathology in pemphigus vulgaris. For induction of blistering, a recombinant single-chain variable fragment (scFv) targeting both Dsg1 and 3 is injected into pieces of human skin (obtained from plastic surgeries). Further characterization of the HSOC model demonstrated that key morphologic, molecular and immunologic features of pemphigus are being replicated. Thus, the pemphigus HSOC model is an excellent alternative to pemphigus animal model systems that are based on the transfer of (auto)antibodies.

OriginalspracheEnglisch
ZeitschriftLaboratory Animals
Jahrgang57
Ausgabenummer4
Seiten (von - bis)381-395
Seitenumfang15
ISSN0023-6772
DOIs
PublikationsstatusVeröffentlicht - 08.2023

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Biomedizintechnik
  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)
  • Zentren: Center for Research on Inflammation of the Skin (CRIS)

DFG-Fachsystematik

  • 205-32 Medizinische Physik, Biomedizinische Technik
  • 205-19 Dermatologie
  • 204-05 Immunologie

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