TY - JOUR T1 - Targeting mitochondrial oxidative stress with MitoQ reduces NET formation and kidney disease in lupus-prone MRL-<em>lpr</em> mice JF - Lupus Science &amp; Medicine JO - Lupus Sci Med DO - 10.1136/lupus-2020-000387 VL - 7 IS - 1 SP - e000387 AU - Karen A Fortner AU - Luz P Blanco AU - Iwona Buskiewicz AU - Nick Huang AU - Pamela C Gibson AU - Deborah L Cook AU - Hege L Pedersen AU - Peter S T Yuen AU - Michael P Murphy AU - Andras Perl AU - Mariana J Kaplan AU - Ralph C Budd Y1 - 2020/04/01 UR - http://lupus.bmj.com/content/7/1/e000387.abstract N2 - Objectives Recent investigations in humans and mouse models with lupus have revealed evidence of mitochondrial dysfunction and production of mitochondrial reactive oxygen species (mROS) in T cells and neutrophils. This can provoke numerous cellular changes including oxidation of nucleic acids, proteins, lipids and even induction of cell death. We have previously observed that in T cells from patients with lupus, the increased mROS is capable of provoking oligomerisation of mitochondrial antiviral stimulator (MAVS) and production of type I interferon (IFN-I). mROS in SLE neutrophils also promotes the formation of neutrophil extracellular traps (NETs), which are increased in lupus and implicated in renal damage. As a result, in addition to traditional immunosuppression, more comprehensive treatments for lupus may also include non-immune therapy, such as antioxidants.Methods Lupus-prone MRL-lpr mice were treated from weaning for 11 weeks with the mitochondria-targeted antioxidant, MitoQ (200 µM) in drinking water. Mice were then assessed for ROS production in neutrophils, NET formation, MAVS oligomerisation, serum IFN-I, autoantibody production and renal function.Results MitoQ-treated mice manifested reduced neutrophil ROS and NET formation, decreased MAVS oligomerisation and serum IFN-I, and reduced immune complex formation in kidneys, despite no change in serum autoantibody .Conclusions These findings reveal the potential utility of targeting mROS in addition to traditional immunosuppressive therapy for lupus. ER -