Dsg1 and Dsg3 Composition of Desmosomes Across Human Epidermis and Alterations in Pemphigus Vulgaris Patient Skin.
adhesion
autoimmune disease (AD)
dermatology
desmoglein
desmosome
epidermis
pemphigus
skin
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
25
02
2022
accepted:
12
04
2022
entrez:
17
6
2022
pubmed:
18
6
2022
medline:
22
6
2022
Statut:
epublish
Résumé
Desmosomes are important epidermal adhesion units and signalling hubs, which play an important role in pemphigus pathogenesis. Different expression patterns of the pemphigus autoantigens desmoglein (Dsg)1 and Dsg3 across different epidermal layers have been demonstrated. However, little is known about changes in desmosome composition in different epidermal layers or in patient skin. The aim of this study was thus to characterize desmosome composition in healthy and pemphigus skin using super-resolution microscopy. An increasing Dsg1/Dsg3 ratio from lower basal (BL) to uppermost granular layer (GL) was observed. Within BL desmosomes, Dsg1 and Dsg3 were more homogeneously distributed whereas superficial desmosomes mostly comprised one of the two molecules or domains containing either one but not both. Extradesmosomal, desmoplakin (Dp)-independent, co-localization of Dsg3 with plakoglobin (Pg) was found mostly in BL and extradesmosomal Dsg1 co-localization with Pg in all layers. In contrast, in the spinous layer (SL) most Dsg1 and Dsg3 staining was confined to desmosomes, as revealed by the co-localization with Dp. In pemphigus patient skin, Dsg1 and Dsg3 immunostaining was altered especially along blister edges. The number of desmosomes in patient skin was reduced significantly in basal and spinous layer keratinocytes with only few split desmosomes found. In addition, Dsg1-Pg co-localization at the apical BL and Dsg3-Pg co-localization in SL were significantly reduced in patients, suggesting that that extradesmosomal Dsg molecules were affected. These results support the hypothesis that pemphigus is a desmosome assembly disease and may help to explain histopathologic differences between pemphigus phenotypes.
Identifiants
pubmed: 35711465
doi: 10.3389/fimmu.2022.884241
pmc: PMC9196036
doi:
Substances chimiques
DSG1 protein, human
0
DSG3 protein, human
0
Desmoglein 1
0
Desmoglein 3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
884241Informations de copyright
Copyright © 2022 Schmitt, Pircher, Steinert, Meier, Ghoreschi, Vielmuth, Kugelmann and Waschke.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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