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J Invest Dermatol. 2016 Jan;136(1):59-66. doi: 10.1038/JID.2015.353.

Super-Resolution Microscopy Reveals Altered Desmosomal Protein Organization in Tissue from Patients with Pemphigus Vulgaris.

Author information

1
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA; Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University School of Medicine, Atlanta, Georgia, USA.
2
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA.
3
Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, USA.
4
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA; Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, USA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA. Electronic address: akowalc@emory.edu.

Abstract

Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease in which autoantibodies (IgG) are directed against the desmosomal cadherin desmoglein 3. To better understand how PV IgG alters desmosome morphology and function in vivo, biopsies from patients with PV were analyzed by structured illumination microscopy, a form of superresolution fluorescence microscopy. In patient tissue, desmosomal proteins were aberrantly clustered and patient IgG colocalized with markers for lipid rafts and endosomes. Additionally, steady-state levels of desmoglein 3 were decreased and desmosomes were reduced in size in patient tissue. Desmosomes at blister sites were occasionally split, with PV IgG decorating the extracellular faces of split desmosomes. Desmosome splitting was recapitulated in vitro by exposing cultured keratinocytes both to PV IgG and to mechanical stress, demonstrating that splitting at the blister interface in patient tissue is due to compromised desmosomal adhesive function. These findings indicate that desmoglein 3 clustering and endocytosis are associated with reduced desmosome size and adhesion defects in tissue of patients with PV. Further, this study reveals that superresolution optical imaging is a powerful approach for studying epidermal adhesion structures in normal and diseased skin.

PMID:
26763424
PMCID:
PMC4730957
DOI:
10.1038/JID.2015.353
[Indexed for MEDLINE]
Free PMC Article

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