Desmosomal proteins in epidermal keratinocytes

Desmosomal proteins are a group of specialized proteins that form desmosomes, which are intercellular junctions essential for the mechanical strength and integrity of the epidermis. In keratinocytes, these proteins—including desmogleins (DSG1-4), desmocollins (DSC1-3), and plaque proteins like desmoplakin (DSP) and plakoglobin (PG)—link the intermediate filament cytoskeleton of adjacent cells, creating a resilient structural network. They play a critical role in maintaining the skin barrier and are involved in signaling pathways that regulate cell proliferation and differentiation. These proteins are the primary targets in autoimmune blistering diseases such as Pemphigus, where autoantibodies disrupt cell-cell adhesion, leading to acantholysis and blister formation. Additionally, genetic mutations in desmosomal genes result in various skin fragility disorders and keratodermas. Therapeutic interventions primarily aim to suppress the production of pathogenic autoantibodies or selectively eliminate the B cells that target these proteins, with novel approaches like DSG3-CAART cells specifically targeting the B-cell receptors for Desmoglein 3.

Other names

DesmosomeDesmosomal complexMacula adhaerensIntercellular bridgesDesmosomal cadherins

B-cell depletion, Inhibition of autoantibody production, FcRn inhibition, Selective depletion of Dsg-reactive B cells, Immunosuppression