Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases

Systemic autoimmune diseases are characterized by the failure of the immune system to differentiate self from non-self. These conditions are associated with significant morbidity and mortality, and they can affect many organs and systems, having significant clinical heterogeneity. Recent discoveries have highlighted that neutrophils, and in particular the neutrophil extracellular traps that they can release upon activation, can have central roles in the initiation and perpetuation of systemic autoimmune disorders and orchestrate complex inflammatory responses that lead to organ damage. Dysregulation of neutrophil cell death can lead to the modification of autoantigens and their presentation to the adaptive immune system. Furthermore, subsets of neutrophils that seem to be more prevalent in patients with systemic autoimmune disorders can promote vascular damage and increased oxidative stress. With the emergence of new technologies allowing for improved assessments of neutrophils, the complexity of neutrophil biology and its dysregulation is now starting to be understood. In this Review, we provide an overview of the roles of neutrophils in systemic autoimmune and autoinflammatory diseases and address putative therapeutic targets that may be explored based on this new knowledge. Neutrophils have a central role in the pathogenesis of systemic autoimmune and autoinflammatory diseases, particularly through neutrophil extracellular trap formation. Recent research suggests novel therapeutics targeting these structures that can improve patient outcomes.

Automated summary

Systemic autoimmune diseases occur when the immune system fails to recognize self from non-self, resulting in significant morbidity and mortality. Neutrophils, especially the neutrophil extracellular traps they release, play a crucial role in the initiation and perpetuation of these diseases, leading to organ damage. Dysregulation of neutrophil cell death can alter autoantigens and trigger complex inflammatory responses. Studies have identified specific neutrophil subsets associated with systemic autoimmune disorders that contribute to vascular damage and oxidative stress. Advances in technology have enhanced our understanding of neutrophil biology and dysregulation. This review provides an overview of the roles of neutrophils in systemic autoimmune and autoinflammatory diseases and explores potential therapeutic targets.