Lupus and proliferative nephritis are PAD4 independent in murine models

• DOI: 10.1172/jci.insight.92926
• Publication Date: 2017-05-17T15:00:52Z
• Authors: Rachael A. Gordon; Jan M. Herter; Florencia Rosetti; Allison M. Campbell; Hiroshi Nishi; Michael Kashgarian; Sheldon I. Bastacky; Anthony Marinov; Kevin M. Nickerson; Tanya N. Mayadas; Mark J. Shlomchik
• Keywords: Nephritis

Though recent reports suggest that neutrophil extracellular traps (NETs) are a source of antigenic nucleic acids in systemic lupus erythematosus (SLE), we recently showed inhibition NETs by targeting the NADPH oxidase complex via cytochrome b-245, β polypeptide (cybb) deletion exacerbated disease MRL.Faslpr mouse model. While these data challenge paradigm promote lupus, it is conceivable global regulatory properties cybb and cybb-independent confound findings. Furthermore, indicate inhibitors peptidyl arginine deiminase, type IV (Padi4), distal mediator NET formation, improve murine models. Here, to clarify contribution SLE, employed genetic approach delete Padi4 model used pharmacological inhibit PADs both anti-glomerular basement membrane proliferative nephritis human-serum-transfer SLE. In contrast prior inhibitor studies, found did not ameliorate any aspect nephritis, loss tolerance, or immune activation. Pharmacological PAD activity had no effect on end-organ damage inducible models glomerulonephritis. These provide direct concept autoimmunity target organ injury