Here we aimed to shed light on the role of the NOX2 complex in handling of secondary necrotic cells (SNECs) and associated consequences for inflammation and autoimmunity during lupus.
This work provides the first, direct comparison of NOX2-dependent (PMA) and NOX2-independent (A23187) NETs using quantitative proteomics, and the first direct comparison of RA and SLE NETs using quantitative proteomics.
Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47<sup>phox</sup> subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the Immunochip in the GTF2IRD1-GTF2I region at 7q11.23 with a complex genomic structure.
Though recent reports suggest that neutrophil extracellular traps (NETs) are a source of antigenic nucleic acids in systemic lupus erythematosus (SLE), we recently showed that inhibition of NETs by targeting the NADPH oxidase complex via cytochrome b-245, β polypeptide (cybb) deletion exacerbated disease in the MRL.Faslpr lupus mouse model.
We found that NCF1 and NADPH oxidase 2 (NOX2) complex-derived ROS is an important regulator of several chronic inflammatory disorders by using models for rheumatoid arthritis, multiple sclerosis, psoriasis and psoriasis arthritis, gout, and lupus.