Bullous Pemphigoid IgG Induces Cell Dysfunction and Enhances the Motility of Epidermal Keratinocytes via Rac1/Proteasome Activation

Frontiers in Immunology
Duerna TieEishin Morita

Abstract

Bullous pemphigoid (BP) is an autoimmune disease characterized by the formation of blisters, in which autoantibodies mainly target type XVII collagen (ColXVII) expressed in basal keratinocytes. BP IgG is known to induce the internalization of ColXVII from the plasma membrane of keratinocytes through macropinocytosis. However, the cellular dynamics following ColXVII internalization have not been completely elucidated. BP IgG exerts a precise effect on cultured keratinocytes, and the morphological/functional changes in BP IgG-stimulated cells lead to the subepidermal blistering associated with BP pathogenesis. Based on the electron microscopy examination, BP IgG-stimulated cells exhibit alterations in the cell membrane structure and the accumulation of intracellular vesicles. These morphological changes in the BP IgG-stimulated cells are accompanied by dysfunctional mitochondria, increased production of reactive oxygen species, increased motility, and detachment. BP IgG triggers the cascade leading to metabolic impairments and stimulates cell migration in the treated keratinocytes. These cellular alterations are reversed by pharmacological inhibitors of Rac1 or the proteasome pathway, suggesting that Rac1 and proteasome activatio...Continue Reading

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Citations

Aug 27, 2019·Frontiers in Immunology·Kata P SzilveszterAttila Mócsai
Jul 18, 2019·Frontiers in Immunology·Giovanni GenoveseAngelo Valerio Marzano

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Methods Mentioned

BETA
biopsies
flow cytometry
Scanning Electron Microscopy
confocal microscopy
Fluorescence microscopy
fluorescence assay
electron microscopy
motility assay

Software Mentioned

ImageJ
Chemotaxis and Migration Tool
ICY
CellProfiler
In Cell Analyzer 1000 Workstation
R
Olympus

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