Experimental lupus is aggravated in mouse strains with impaired induction of neutrophil extracellular traps

Cleaved N-terminal histone tails distinguish between NADPH oxidase (NOX)-dependent and NOX-independent pathways of neutrophil extracellular trap formation

“…Notably, depending of the nature of immune complexes, also NOX-dependent NET formation may occur 46. The fact that circulating NETs in SLE appear to have been generated through a NOX-independent pathway may explain why NOX deficiency, potentially reducing NOX-dependent NET formation, does not ameliorate disease activity in MRL/lpr mice,47 nor in a pristane-induced lupus model 48. Similarly, the finding that individuals with chronic granulomatous disease, that is, patients who fail to produce ROS through NOX, have a propensity of developing SLE has questioned the involvement of NOX-dependent NET formation in SLE 49–51…”

IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation

“…However, a number of studies have suggested that there is no role for neutrophil NETosis in the pathogenesis of lupus using MRL.Fas lpr mice crossed to either Pad4-or Nox2-deficient animals. Loss of Nox2 and NADPH oxidase activity resulted in an exacerbation of kidney disease (59), whereas PAD4 deficiency had no effect on glomerulonephritis in the MRL.Fas lpr model (60) but exacerbated both kidney disease and ANA production in pristane-induced lupus (61). Thus, further work is required to elucidate the role of neutrophils in end-organ disease and their contribution to autoimmune lung specifically.…”

Self-dsDNA in the pathogenesis of systemic lupus erythematosus

“…The uptake of NETs by macrophages does not induce proinflammatory cytokine secretion, indicating that this process is immunologically silent [17]. A defect in this process will cause the accumulation of autoantigens including dsDNA [18][19][20], although another study has shown a protective role of NETs in SLE [21]. Recently, emerging evidence indicates that self-dsDNA released from cell death plays a crucial role in SLE pathogenesis (Fig.…”