Extracellular Vesicles in Inflammation

All living organisms depend on the ability to protect themselves from pathogens and to repair tissue damage resulting from infection or trauma. An adequate inflammatory response is thus critical for survival. Maladaptive regulation of inflammation, however, can have devastating consequences for the organism. It can either result in an acute systemic inflammatory response (sepsis) or in non-resolving inflammation driving a number of widespread chronic diseases. Inflammation-related disorders represent a major challenge for global healthcare, as more than 50% of all deaths worldwide are attributable to acute and chronic inflammation. Extracellular vesicles (EVs), a heterogeneous group of tiny membrane-enclosed particles released by cells into the extracellular environment, are emerging as important regulators of inflammation. They are involved in homeostatic processes, such as the activation of blood clotting and the rapid removal of unnecessary molecules from cells. They act as shuttle systems to enable communication between cells and modulate the functions of their target cells by delivering intercellular signals via their molecular cargo. Depending on the cell type from which they originate, as well as on their microenvironment and the conditions under which they are released, EVs can differ in their immunomodulatory properties. Boosted by their high potential for diagnostic and therapeutic applications, EVs have become a hot topic in science. Recognizing the significance of EVs in modulating inflammation, the University for Continuing Education Krems, the IMC University of Applied Sciences Krems, and the Medical University of Vienna have jointly established the first doctoral program focusing on the biological importance of EVs and their functional roles in inflammation. Our central objective is to gain a better understanding of inflammation from a systemic perspective and how it is modulated by EVs. As the potential involvement of EVs in transfusion-related adverse events is increasingly recognized, we will study the effects of processing and storage of the most commonly transfused blood products, red blood cells and platelet concentrates, on the release and functional characteristics of EVs. Five PhD projects will investigate different aspects of the immunomodulatory function of EVs, their effects on different target cells in the vasculature, as well as the underlying mechanisms. This may yield novel strategies to mitigate adverse events of blood transfusion, to ensure product quality, and to support patient blood management.