Neutrophil activation in disease An unexpected journey

The immune system, is a complex system that protects us against pathogens. It consists of a variety of immune cells and it can be divided into the innate and adaptive systems. Cells belonging to the innate system react quickly to an invading pathogen. Cells belonging to the adaptive system react slower, but more specific. Immune system dysregulation can result in autoimmune diseases and excessive damage to healthy cells during severe infections. This thesis focuses on neutrophils, vital cells of the innate immune system. The main task of neutrophils is eliminating pathogens. In order to do so, neutrophils employ various mechanisms upon activation, including degranulation, reactive oxygen species production, phagocytosis, NETosis, mediator release, and extracellular vesicle secretion. It used to be thought that the only job of neutrophils was to destroy pathogens and that they didn’t have other functions. However, in recent years it has become clear that they are also important in the communication with other immune cells. One important mechanism of cellular communication is via the release of extracellular vesicles.
This thesis explored the role of neutrophil activation as well as the effect of extracellular vesicles of neutrophils on the function of cells of the adaptive immune system. This was done specifically in the context of arthritis, including rheumatoid arthritis and spondyloarthritis, and COVID-19. Two different diseases in which neutrophil (over)activation plays an important role. Insights gained from this study could potentially have implications for designing therapeutic strategies to modulate immune responses.