Electron microscopy of desmosomal structures in the pemphigus human skin organ culture model

Uta Katharina Radine; Valéria Bumiller-Bini Hoch; Angelica B.Winter Boldt; Detlef Zillikens; Ralf J. Ludwig; Christoph M. Hammers; Matthias Klinger; Jennifer E. Hundt

doi:10.3389/fmed.2022.997387

Electron microscopy of desmosomal structures in the pemphigus human skin organ culture model

Uta Katharina Radine, Valéria Bumiller-Bini Hoch, Angelica B.Winter Boldt, Detlef Zillikens, Ralf J. Ludwig, Christoph M. Hammers, Matthias Klinger, Jennifer E. Hundt^*

^*Corresponding author for this work

Federal University of Paraná

Abstract

Pemphigus is a chronic autoimmune skin blistering disease, characterized by acantholysis and by the production of autoantibodies directed against the structural desmosomal proteins desmoglein 1 (DSG1) and/or DSG3. Model systems allow the identification and testing of new therapeutic targets. Here, we evaluated ultrastructural desmosomal morphology in the human skin organ culture (HSOC) model injected with either anti-desmoglein (DSG) 1/3 single-chain variable fragment (scFv, termed Px4-3), Staphylococcus aureus exfoliative toxin (ETA) as a reference and positive control, and normal human IgG as a negative control. Each experimental condition was evaluated in abdominal skin biopsies from five different donors. After 24 h of incubation, we processed the samples for histological and ultrastructural electron microscopy analyses. We found that Px4-3 or ETA induced a loss of desmosomes and increased interdesmosomal widening, similar to patient skin biopsies and other pemphigus models. Thus, we propose the HSOC pemphigus model as an attractive tool to unravel novel therapeutic targets.

Original language	English
Article number	997387
Journal	Frontiers in medicine
Volume	9
ISSN	2296-858X
DOIs	https://doi.org/10.3389/fmed.2022.997387
Publication status	Published - 14.11.2022

Funding

This study was supported by a SNF grant dedicated to RL and JH (CRSII5_202301/1); in addition, by the Research Training Group “Modulation of Autoimmunity” (GRK 1727) and the Excellence Cluster “Precision Medicine in Chronic Inflammation” (EXC 2167), both from the Deutsche Forschungsgemeinschaft, as well as a scholarship provided by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) to VB-BH and a short-term research grant Brazil to VB-BH by Deutscher Akademischer Austauschdienst (DAAD). AB received a research productivity scholarship from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (protocol number: 314288/2018-0). The funding agencies had no role in study design, sample collection, data analysis, and interpretation as well as manuscript drafting and submission.

Research Areas and Centers

Centers: Center for Research on Inflammation of the Skin (CRIS)
Academic Focus: Biomedical Engineering

DFG Research Classification Scheme

2.21-05 Immunology
2.22-19 Dermatology
2.22-32 Medical Physics, Biomedical Technology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fmed.2022.997387

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@article{b4e37db2fca0400da20f07ee487e6887,

title = "Electron microscopy of desmosomal structures in the pemphigus human skin organ culture model",

abstract = "Pemphigus is a chronic autoimmune skin blistering disease, characterized by acantholysis and by the production of autoantibodies directed against the structural desmosomal proteins desmoglein 1 (DSG1) and/or DSG3. Model systems allow the identification and testing of new therapeutic targets. Here, we evaluated ultrastructural desmosomal morphology in the human skin organ culture (HSOC) model injected with either anti-desmoglein (DSG) 1/3 single-chain variable fragment (scFv, termed Px4-3), Staphylococcus aureus exfoliative toxin (ETA) as a reference and positive control, and normal human IgG as a negative control. Each experimental condition was evaluated in abdominal skin biopsies from five different donors. After 24 h of incubation, we processed the samples for histological and ultrastructural electron microscopy analyses. We found that Px4-3 or ETA induced a loss of desmosomes and increased interdesmosomal widening, similar to patient skin biopsies and other pemphigus models. Thus, we propose the HSOC pemphigus model as an attractive tool to unravel novel therapeutic targets.",

author = "Radine, \{Uta Katharina\} and \{Bumiller-Bini Hoch\}, Val{\'e}ria and Boldt, \{Angelica B.Winter\} and Detlef Zillikens and Ludwig, \{Ralf J.\} and Hammers, \{Christoph M.\} and Matthias Klinger and Hundt, \{Jennifer E.\}",

note = "Publisher Copyright: Copyright {\textcopyright} 2022 Radine, Bumiller-Bini Hoch, Boldt, Zillikens, Ludwig, Hammers, Klinger and Hundt.",

year = "2022",

month = nov,

day = "14",

doi = "10.3389/fmed.2022.997387",

language = "English",

volume = "9",

journal = "Frontiers in medicine",

issn = "2296-858X",

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TY - JOUR

T1 - Electron microscopy of desmosomal structures in the pemphigus human skin organ culture model

AU - Radine, Uta Katharina

AU - Bumiller-Bini Hoch, Valéria

AU - Boldt, Angelica B.Winter

AU - Zillikens, Detlef

AU - Ludwig, Ralf J.

AU - Hammers, Christoph M.

AU - Klinger, Matthias

AU - Hundt, Jennifer E.

PY - 2022/11/14

Y1 - 2022/11/14

N2 - Pemphigus is a chronic autoimmune skin blistering disease, characterized by acantholysis and by the production of autoantibodies directed against the structural desmosomal proteins desmoglein 1 (DSG1) and/or DSG3. Model systems allow the identification and testing of new therapeutic targets. Here, we evaluated ultrastructural desmosomal morphology in the human skin organ culture (HSOC) model injected with either anti-desmoglein (DSG) 1/3 single-chain variable fragment (scFv, termed Px4-3), Staphylococcus aureus exfoliative toxin (ETA) as a reference and positive control, and normal human IgG as a negative control. Each experimental condition was evaluated in abdominal skin biopsies from five different donors. After 24 h of incubation, we processed the samples for histological and ultrastructural electron microscopy analyses. We found that Px4-3 or ETA induced a loss of desmosomes and increased interdesmosomal widening, similar to patient skin biopsies and other pemphigus models. Thus, we propose the HSOC pemphigus model as an attractive tool to unravel novel therapeutic targets.

AB - Pemphigus is a chronic autoimmune skin blistering disease, characterized by acantholysis and by the production of autoantibodies directed against the structural desmosomal proteins desmoglein 1 (DSG1) and/or DSG3. Model systems allow the identification and testing of new therapeutic targets. Here, we evaluated ultrastructural desmosomal morphology in the human skin organ culture (HSOC) model injected with either anti-desmoglein (DSG) 1/3 single-chain variable fragment (scFv, termed Px4-3), Staphylococcus aureus exfoliative toxin (ETA) as a reference and positive control, and normal human IgG as a negative control. Each experimental condition was evaluated in abdominal skin biopsies from five different donors. After 24 h of incubation, we processed the samples for histological and ultrastructural electron microscopy analyses. We found that Px4-3 or ETA induced a loss of desmosomes and increased interdesmosomal widening, similar to patient skin biopsies and other pemphigus models. Thus, we propose the HSOC pemphigus model as an attractive tool to unravel novel therapeutic targets.

UR - https://www.scopus.com/pages/publications/85142692399

U2 - 10.3389/fmed.2022.997387

DO - 10.3389/fmed.2022.997387

M3 - Journal articles

AN - SCOPUS:85142692399

SN - 2296-858X

VL - 9

JO - Frontiers in medicine

JF - Frontiers in medicine

M1 - 997387

ER -

Electron microscopy of desmosomal structures in the pemphigus human skin organ culture model

Abstract

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Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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