interleukin-8 and Epidermolysis-Bullosa

Pemphigoid diseases refer to a group of severe autoimmune skin blistering diseases characterized by subepidermal blistering and loss of dermal-epidermal adhesion induced by autoantibody and immune cell infiltrate at the dermal-epidermal junction and upper dermis. Here, we explore the role of the immune cell-secreted serine protease, granzyme B, in pemphigoid disease pathogenesis using three independent murine models. In all models, granzyme B knockout or topical pharmacological inhibition significantly reduces total blistering area compared to controls. In vivo and in vitro studies show that granzyme B contributes to blistering by degrading key anchoring proteins in the dermal-epidermal junction that are necessary for dermal-epidermal adhesion. Further, granzyme B mediates IL-8/macrophage inflammatory protein-2 secretion, lesional neutrophil infiltration, and lesional neutrophil elastase activity. Clinically, granzyme B is elevated and abundant in human pemphigoid disease blister fluids and lesional skin. Collectively, granzyme B is a potential therapeutic target in pemphigoid diseases.

Topics: Animals; Autoantigens; Autoimmune Diseases; Blister; Chemokine CXCL2; Chemotactic Factors; Collagen Type XVII; Disease Models, Animal; Epidermolysis Bullosa; Granzymes; Humans; Inflammation; Integrin alpha6; Interleukin-8; Neutrophil Infiltration; Non-Fibrillar Collagens; Pemphigoid, Bullous; Severity of Illness Index

Topics: Blister; Body Fluids; Epidermolysis Bullosa; Humans; Interleukin-8; Matrix Metalloproteinase 9