Background/Purpose: Systemic Lupus Erythematosus (SLE) is characterized by a type I Interferon (IFN-I) gene signature in peripheral blood lymphocytes (PBL), which contain enlarged mitochondria and reactive oxygen species (ROS).  SLE patients also manifest an unusual population of CD4-CD8- T cells that arise during homeostatic proliferation of CD8+ T cells. We have previously shown that ROS is sufficient to induce oligomerization of MAVS (mitochondrial antiviral stimulator) and type I Interferon (IFN-I) production, both of which was reversible with the mitochondrially targeted antioxidant, MitoQ. In addition, SLE patients manifested spontaneous MAVS oligomerization.  CD4-CD8- T cells from MRL-lpr mice also manifested spontaneous oligomerization of MAVS and an IFN-I gene signature.  Based on these collective observations, we elected to test the therapeutic potential of MitoQ in lupus-prone MRL-lpr mice.    

Methods: MitoQ was administered in drinking water (200 or 400 mM) to MRL-lpr mice from weaning for the next 11 weeks.

Results: MitoQ produced a reduction in MAVS oligomerization in CD4-CD8- T cells and serum IFN-I.  There was no effect on adenopathy or autoantibody production, but MitoQ did result in decreased dermatitis, immune complex deposition in kidneys, and NETosis (Fig.1).

Conclusion: These findings suggest that SLE may be in part a disorder of mitochondrial dysfunction and ROS production, contributing to MAVS oligomerization and IFN-I stimulation.  It also suggests mitochondrially targeted antioxidants as a therapeutic intervention for SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/treatment-of-lupus-prone-mrl-lpr-mice-with-the-mitochondrial-antioxidant-mitoq/