Skin Blistering and Collagens: From Bench to Therapies

The skin is a multifunctional organ. Of its functions, the perhaps most evident one is that of being a flexible, mechanically robust barrier. This is achieved through a two-compartment arrangement with the skin’s outermost compartment, the epidermis being the principal barrier and the inner dermis providing flexibility and tensile strength. Tight, durable joining of the two compartments is crucial and is achieved through the dermal–epidermal junction zone. Two specialized collagens, the large collagen VII and the transmembrane collagen XVII are essential for the mechano-resilience of this zone. The importance of these two collagens is evident from genetic and autoimmune skin blistering diseases occurring as consequence of their genetic deficiency or antibody targeting. Here, we will provide a detailed overview of the biology of collagen VII and XVII—from biosynthesis to their roles in human physiology and pathophysiology, which span beyond the skin.