Lupus neutrophils: 'NET' gain in understanding lupus pathogenesis

Historically, researchers have focused on the role of adaptive immunity in lupus pathogenesis; recently, however, there has been renewed interest in the contributions of a prototypical innate immune cell - the neutrophil.

Neutrophil extracellular traps (NETs) are released via a novel form of cell death called NETosis. NETs, consisting of a chromatin meshwork decorated with antimicrobial peptides, play an important role in the innate response to microbial infections. Some lupus patients do not clear NETs normally, a phenotype that correlates with disease activity. Further, lupus neutrophils - and, in particular, an aberrant subset called low-density granulocytes - have an increased propensity to undergo NETosis. Both interferon alpha (IFNα) and immune complexes are potential triggers of enhanced NETosis in lupus patients.

NETs are a potent stimulus for IFNα release by plasmacytoid dendritic cells, and, as such, may play an important role in propagation of the lupus phenotype. NETs can also directly damage tissues - including the endothelium - with implications for lupus nephritis and accelerated atherosclerosis. Whether aberrant NETosis is sufficient to trigger systemic lupus erythematosus, and whether inhibition of NETosis can ameliorate clinical manifestations of lupus, are open questions, and will be exciting topics of future research.