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Christian Lood, PhD

Research Assistant Professor

University of Washington



Impaired Mitochondrial Clearance in Systemic Lupus Erythematosus

The energy our cells need comes from structures known as mitochondria that serve as power plants. Dr. Lood recently found that some immune cells throw out their mitochondria, which trigger inflammation and promote development of disease. In the current study he proposes to investigate how the body normally disposes of the released mitochondria so that they don’t cause inflammation and find out if those cleanup mechanisms don’t work well in lupus patients. Those results may provide new opportunities for developing lupus therapies, as well as identify novel biomarkers to monitor, and potentially predict, development of disease.


What this study means to people with lupus

Dr. Lood’s group discovered a new cause for the out-of control inflammation of lupus. Certain immune cells normally eject the mitochondria power plants that provide them with energy. The team is exploring a new treatment approach by examining whether people with lupus do not properly remove mitochondria, thus sparking inflammation. This highly novel project is likely to lead to new targets for therapy and new biomarkers for evaluating disease progression and response to treatment.


We recently described a fundamental role for mitochondrial-mediated inflammation in systemic lupus erythematosus. Briefly, mitochondrial ROS promoted release of mitochondria and oxidized mitochondrial DNA inducing prominent IFN-beta production through the cGAS-STING pathway propagating disease in lupus-prone mice. However, although known to promote inflammation, mechanisms contributing to mitochondrial clearance have not been investigated. The overall aims of the present study are to investigate molecular events participating in the clearance of mitochondria in lupus pathogenesis as well as identifying mitochondrial biomarkers associated with disease activity and severity. In the first aim we will investigate if lupus patients have increased levels of cell-free mitochondria and their relation to inflammatory markers, as well as disease activity and severity. In the second aim we will assess mitochondrial clearance, in particular phagocytosis and cytokine induction, by myeloid cells. As complement components are known to regulate uptake and inflammatory properties of apoptotic cells and immune complexes, we will determine the role of complement in mitochondrial clearance and inflammatory potential. Finally, we will characterize anti-mitochondrial antibodies in SLE patients, including their inflammatory potential and capacity to stratify patients based on disease phenotype. In summary, the current research will provide novel, much needed, insight into mitochondrial-mediated inflammation and autoimmunity in lupus patients.

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