@article {Fortnere000387, author = {Karen A Fortner and Luz P Blanco and Iwona Buskiewicz and Nick Huang and Pamela C Gibson and Deborah L Cook and Hege L Pedersen and Peter S T Yuen and Michael P Murphy and Andras Perl and Mariana J Kaplan and Ralph C Budd}, title = {Targeting mitochondrial oxidative stress with MitoQ reduces NET formation and kidney disease in lupus-prone MRL-lpr mice}, volume = {7}, number = {1}, elocation-id = {e000387}, year = {2020}, doi = {10.1136/lupus-2020-000387}, publisher = {Archives of Disease in childhood}, abstract = {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 {\textmu}M) 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.}, URL = {https://lupus.bmj.com/content/7/1/e000387}, eprint = {https://lupus.bmj.com/content/7/1/e000387.full.pdf}, journal = {Lupus Science \& Medicine} }