Neutrophil extracellular traps in autoimmunity, renal diseases, and transplantation

Autoimmunity is a significant cause of renal dysfunction and organ failure as immune responses directed against self-antigens often target the kidney. Neutrophils are effector cells that protect the host against extracellular pathogens as part of the acute inflammatory response. However, neutrophils exhibit abnormal phenotypes under systemic autoimmunity conditions and promote immune dysregulation by releasing proinflammatory mediators, cytotoxic granule proteins, and neutrophil extracellular traps (NETs). During NETosis, nuclear and cytoplasmic content combines to release chromatin fibers decorated with granule proteins. NETs induced by different stimuli vary in composition, and some of the molecules externalized can behave as autoantigens involved in the development of autoimmune responses in predisposed subjects. Additionally, impaired NET degradation increases the immune system’s exposure to these modified autoantigens, thus augmenting NET-induced organ injury. Thus, autoimmunity research is essential for translational nephrology. Multiple experimental studies have revealed unexpected molecular mechanisms linking NETosis with autoimmune disease and renal dysfunction. This chapter summarizes the relationship between NETs, autoimmunity, and kidney disease, highlighting the translational aspects of NET-associated autoimmunity.