Proteins derived from neutrophil extracellular traps may serve as self-antigens and mediate organ damage in autoimmune diseases

Abstract

Neutrophils are the most abundant leukocytes in circulation and represent one of the first lines of defense against invading pathogens. Neutrophils possess a vast arsenal of antimicrobial proteins, which can be released from the cell by a death program termed NETosis. Neutrophil extracellular traps (NETs) are web-like structures consisting of decondensed chromatin decorated with granular and cytosolic proteins. Both exuberant NETosis and impaired clearance of NETs have been implicated in the organ damage of autoimmune diseases, such as systemic lupus erythematosus (SLE), small vessel vasculitis (SVV), and psoriasis. NETs may also represent an important source of modified autoantigens in SLE and SVV. Here, we review the autoimmune diseases linked to NETosis, with a focus on how modified proteins externalized on NETs may trigger loss of immune tolerance and promote organ damage.

Keywords: NETs; autoimmunity; citrullination; neutrophil; posttranslational modifications; psoriasis; systemic lupus erythematosus (SLE); vasculitis.

Figure 1

Circulating lupus LDGs undergo increased NETosis. (A) Representative images of control neutrophils, lupus neutrophils, and lupus LDGs isolated from peripheral blood and analyzed at baseline (T0) or after stimulation for 2 h with DMSO or PMA. Panels show merged images of neutrophil extracellular traps (NETs) in which neutrophil elastase is stained green by immunofluorescence and DNA is stained blue by Hoechst 33342; 40× images, scale bar: 20 μm. (B) Quantification of the percentage of NETs (elastase-labeled cells over total number of cells) are plotted as mean ± SEM (n = 6 patients/group; ^*p = 0.05). [Obtained with permission from Villanueva et al. (2011) and The Journal of Immunology. Copyright 2011. The American Association of Immunologists, Inc.].