A Well-Intentioned Enemy in Autoimmune and Autoinflammatory Diseases: NETosis

Abstract

Neutrophils are an essential member of the innate immune system derived from the myeloid stem cell series and develop in the bone marrow. The action of neutrophils defined in immune response includes phagocytosis, degranulation, cytokine production, and neutrophil extracellular traps. The success of the host immune defense depends on effective neutrophil activation. Recent studies have shown that neutrophils that have completed their task in the field of inflammation rejoin circulation. Uncontrolled inflammatory response and dysregulated immune responses to the host are important factors in the development of acute and chronic diseases. Neutrophils are the first cells to be drawn into the field at the time of inflammation. They have developed response strategies that produce proinflammatory cytokines and are known as neutrophil extracellular traps since they create mesh-like structures with their DNA contents into the external environment and release their granular proteins in this way. This article summarizes numerous recent studies and reviews the role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases in the hope, that this will lead to the development of more effective treatments. In addition, in this review, the role of neutrophil extracellular trap formation in some pediatric autoimmune diseases is emphasized.

Figure 1.

NETosis is of 2 types, suicidal and vital, according to whether the cell integrity of neutrophils is disturbed or not. Suicidal NETosis is the inability of the cell to perform its missions, such as migration and phagocytosis. Since this is a type of cell suicide, cellular kamikaze has also been used to refer to suicidal NETosis. In suicidal NETosis, the nuclear membrane integrity of the cell is impaired, and cytoplasmic chromatin condensation and plasma membrane explosion are also observed. In vital NETosis, no plasma membrane damage or cellular breakdown (lysis) is observed. Neutrophils under vital NETosis begin to become anuclear; nonetheless, plasma membrane integrity is maintained, motility persists, and neutrophils do not lose their ability to phagocytosis. In recent proteomics analyses, neutrophil extracellular traps (NETs) were induced ex vivo by phorbol 12 myristate 13 acetate (PMA), IL-8. After all, according to recent research, lipopolysaccharide (LPS) and β-glucan stimulation have been reported to be important in vital NETosis. Created with BioRender.com.