Desmogleinmediated

Desmoglein-mediated refers to the biological processes governed by the desmoglein family of cadherin proteins that are components of desmosomes. Desmogleins, including desmoglein-1, -2, -3, and -4, mediate calcium-dependent cell–cell adhesion in epithelial and other tissues and participate in signaling pathways that influence keratinocyte behavior, tissue integrity, and wound responses.

Desmogleins are expressed in stratified epithelia with distinct patterns: desmoglein-1 is abundant in the upper epidermal layers, desmoglein-3 is prominent in mucosal and lower epidermal layers, and other family members contribute to adhesion in various tissues. Disruption of desmoglein function weakens intercellular cohesion and can alter keratinocyte signaling, affecting barrier function and tissue homeostasis.

In pathology, desmoglein-mediated processes are central to autoimmune diseases such as pemphigus. Autoantibodies against desmoglein-1 and desmoglein-3 are characteristic: anti-Dsg1 is associated with pemphigus foliaceus, while anti-Dsg3 (often with anti-Dsg1) underlies pemphigus vulgaris. Binding of autoantibodies triggers antigenic modulation, internalization, and degradation of desmogleins, leading to desmosome disassembly, acantholysis, and loss of cell–cell adhesion. This is accompanied by keratinocyte signaling changes, including activation of variants of MAP kinase pathways, contributing to blister formation.

Clinically, desmoglein-mediated autoimmunity manifests as mucocutaneous blisters and erosions in pemphigus forms. Diagnosis relies on serology for anti-Dsg1/DSG3 antibodies and immunofluorescence showing intercellular IgG deposition. Treatments aim to suppress autoantibody production and desmoglein-directed pathology, with corticosteroids, immunosuppressants, and rituximab as common options. Genetic mutations in desmoglein genes can cause skin fragility disorders, highlighting the broader role of desmoglein-mediated adhesion beyond autoimmunity.