Pathomechanisms or local inflammatory tissue priming in Pyoderma gangraenosum
Chronic inflammatory diseases are often heralded by repeated recurrence of acute inflammatory bouts occurring at specific sites previously already affected by inflammation or injury. The fact that these sites are for some reason more prone to inflammation recurrence suggests the existence of tissue priming, a kind of trained immunity of local tissue (Friscic et al. Immunity 2021; Friscic et al, Curr Opin Immunol 2022). During tissue priming, cells change their functional status, causing invigorated response to a second challenge which often has additive or synergistic effect with the first. In context of local tissue priming in chronic inflammatory diseases of the skin, an important place takes phenomenon of pathergy. This term is used to describe hyper-reactivity of the skin that occurs in response to even minor trauma, leading to an exaggerated inflammatory cutaneous response. One of the prototypic disorders characterized by pathergy is Pyoderma gangraenosum (PG). This inflammatory disease of unknown aetiology is characterized by chronic, recurrent ulcerations of the skin, most commonly affecting the trunk and lower extremities and often occuring with concomitant autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease, suggesting an autoinflammatory cause. Although it was first described over a century ago, the pathophysiology of PG is still poorly understood. In a project funded by the University of Lübeck (Funds for yoing academic, granted to Jasna Friščić) we explore the aspect of inflammatory tissue priming and the role of local stromal tissue in disease development and conveyance of chronic inflammation in PG. The final goal is to provide a basis for new therapies and approaches in PG disease management.