The Role of Neutrophils and NETosis in Diseases: The Implications for Therapy.

Neutrophils are the most abundant innate immune cells and are pivotal first responders in host defense, playing an important role in maintaining body homeostasis and regulating pathological conditions. Growing evidence indicates that neutrophils exhibit functional heterogeneity and participate in immune regulation through processes such as neutrophil extracellular trap formation (NETosis). These findings have expanded the traditional view of neutrophils as short-lived effector cells. Nevertheless, how distinct neutrophil states are temporally coordinated during disease development, and how this coordination may be therapeutically exploited, remains insufficiently understood. In this review, we provide a comprehensive overview of neutrophil biology, focusing on functional heterogeneity, NETosis, and their roles in infectious diseases, autoimmune disorders, and cancers. We further discuss emerging therapeutic strategies targeting neutrophils, as well as advanced technologies that have enabled high-resolution characterization of neutrophil states and functions. Building on the evidence above, the concept of "neutrophil immune clock" is proposed to describe the temporal changes in neutrophil-mediated immune responses. A time-resolved perspective on neutrophil responses may offer new insights into disease progression and support the development of neutrophil-targeted strategies for disease prevention and therapy.