Superficial dsg2 expression limits epidermal blister formation mediated by pemphigus foliaceus antibodies and exfoliative toxins.

Dermatology Research and Practice
Donna BrennanMy G Mahoney

Abstract

Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF) and staphylococcal scalded skin syndrome (SSSS) are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1). To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg) mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT) mice were injected with purified ETA or PF Ig. We showed that ectopic expression of Dsg2 reduced the extent of blister formation in response to both ETA and PF Ig. In response to PF Ig, we observed either a dramatic loss or a reorganization of Dsg1-alpha, Dsg1-beta, and, to a lesser extent, Dsg1-gamma, in WT mice. The Inv-Dsg2 Tg mice showed enhanced retention of Dsg1 at the cell-cell border. Collectively, our data support the role for Dsg2 in cell adhesion and suggest that ectopic superficial expression of Dsg2 can increase membrane preservation of Dsg1 and limit epidermal blister forma...Continue Reading

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Citations

Feb 17, 2018·Frontiers in Immunology·Volker Spindler, Jens Waschke
Nov 12, 2013·Cell Communication & Adhesion·Robert M Harmon, Kathleen J Green
Jan 28, 2014·Cell Communication & Adhesion·Volker Spindler, Jens Waschke
Nov 26, 2015·Seminars in Immunopathology·Giovanni Di ZenzoLuca Borradori
Nov 17, 2020·Frontiers in Immunology·Anna M SigmundFranziska Vielmuth
Aug 27, 2021·Frontiers in Medicine·Thomas Schmitt, Jens Waschke

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Methods Mentioned

BETA
transgenic
biopsies
fluorescence microscopy

Software Mentioned

Phase 3 Imaging Systems

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