Neutrophil Extracellular Traps (NETs) in Sterile Inflammatory Diseases

Abstract

Neutrophil Extracellular Traps (NETs) are fibrous web-like structures released by neutrophils in response to pathogenic infections or inflammatory stimuli. Composed of decondensed chromatin DNA, histones, and granular proteins, NETs primarily function to eliminate pathogens through physical entrapment and biochemical cytotoxicity. However, they may also contribute to the pathogenesis of inflammatory diseases. While NETs played an important role in pathogen defense, their non-specific components can also damage surrounding tissues, exacerbating inflammation. The role and mechanisms of NETs in various diseases have been well-documented, including autoimmune diseases, cancer, and infectious diseases. This review aims to elaborate on the mechanisms by which NETs mediate sterile inflammation.

Keywords: ICIs; autoimmune diseases; extracellular traps; immune checkpoint inhibitors; neutrophils; sterile inflammation.

Figure 1

NETosis. Neutrophils trigger NETosis after being stimulated by platelets, pathogens, autoantibodies, cytokines, etc. in vivo and by PMA and ionomycin in in vitro experiments. NETosis could be further subdivided into Lytic NETosis, Vital NETosis, and mitochondrial NETosis according to different mechanisms of generating NETs.

Figure 2

The mechanism by which NETs mediate sterile inflammation. NETs cause the occurrence of sterile inflammation and amplify the inflammation itself through ways such as damaging tissues with their own components, stimulating the production of inflammatory factors, forming complexes with autoantibodies, and activating immune cells.