Neutrophils in Inflammatory Diseases: Unraveling the Impact of Their Derived Molecules and Heterogeneity

Inflammatory diseases involve numerous disorders and medical conditions defined by an insufficient level of self-tolerance. These diseases evolve over the course of a multi-step process through which environmental variables play a crucial role in the emergence of aberrant innate and adaptive immunological responses. According to experimental data accumulated over the past decade, neutrophils play a significant role as effector cells in innate immunity. However, neutrophils are also involved in the progression of numerous diseases through participation in the onset and maintenance of immune-mediated dysregulation by releasing neutrophil-derived molecules and forming neutrophil extracellular traps, ultimately causing destruction of tissues. Additionally, neutrophils have a wide variety of functional heterogeneity with adverse effects on inflammatory diseases. However, the complicated role of neutrophil biology and its heterogeneity in inflammatory diseases remains unclear. Moreover, neutrophils are considered an intriguing target of interventional therapies due to their multifaceted role in a number of diseases. Several approaches have been developed to therapeutically target neutrophils, involving strategies to improve neutrophil function, with various compounds and inhibitors currently undergoing clinical trials, although challenges and contradictions in the field persist. This review outlines the current literature on roles of neutrophils, neutrophil-derived molecules, and neutrophil heterogeneity in the pathogenesis of autoimmune and inflammatory diseases with potential future therapeutic strategies.