Anti-dsDNA antibodies bind to TLR4 and activate NLRP3 inflammasome in lupus monocytes/macrophages

摘要: NLRP3 inflammasome has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The activation results production IL-1β and subsequent inflammation. Anti-dsDNA antibodies (anti-dsDNA Abs) play critical roles development progression SLE. However, mechanism SLE is still not known. This study investigated stimulated by anti-dsDNA Abs monocytes/macrophages from patients. Monocytes/macrophages patients or healthy controls were with Ab-positive serum purified Abs. Activation was measured flow cytometry Western blot. isolated active injected into female (NZB × NZW) F1 mice frequencies Th17 Treg examined. activity caspase-1 significantly increased correlated levels disease activities. concentrations IL-17A also higher compared to controls. rather than RF (rheumatoid factor)-positive monocytes. bound TLR4 on macrophages induced ROS. Mitochondria-targeting antioxidant Mito-TEMPO, IκB kinase inhibitor peptide siRNA inhibited secretion Injection resulted IL-17A. Th17/Treg cell ratio following Ab injection. activated binding inducing mitochondrial