# Caspase-activation powers anti-Desmoglein 3-induced acantholysis in human epidermis

## TL;DR

This study shows that caspase activation works with anti-Dsg3 antibodies to cause cell separation in a skin disease called pemphigus vulgaris.

## Contribution

The study reveals a dual mechanism involving caspase activation and Dsg3 redistribution in pemphigus vulgaris acantholysis.

## Key findings

- Anti-Dsg3 antibodies cause acantholysis by redistributing Dsg3 to intracellular compartments without caspase activation.
- FasL-induced caspase activation synergistically enhances cell adhesion loss by cleaving Dsg3.
- The findings suggest a dual mechanism contributing to disease heterogeneity in pemphigus vulgaris.

## Abstract

Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease caused by circulating autoantibodies against desmoglein (Dsg) 1 and Dsg 3. Whether acantholysis in PV results exclusively from antibody binding to Dsgs or involves additional factors remains controversial. Given that Fas-Ligand (FasL), an activator of apoptotic caspase-8, is increased in the serum and the skin of patients with PV, we investigated the role of caspases in anti-Dsg3-mediated acantholysis using both ex vivo and in vitro models. Our results demonstrated that anti-Dsg3 antibodies induced acantholysis ex vivo in the absence of caspase activation, primarily through the redistribution of Dsg3 to intracellular compartments. FasL-induced caspase activation led to a synergistic amplification of anti-Dsg3-mediated loss of cell adhesion by promoting Dsg3 cleavage. This dual mechanism provides new insights into the disease heterogeneity of PV.