Associated TP17: The role of mitochondrial DNA in autoimmune skin blistering diseases

Mitochondrial dysfunction is thought to contribute to autoimmunity as well as neurodegenerative andmetabolic disorders and infection. The most likely mechanism is the increased production of reactiveoxygen species (ROS) and its downstream effects on the cells affected. The mitochondrial proteinsinvolved are either encoded by the mitochondrial and nuclear genomes. Most studies analyzing the role of the mitochondria in autoimmunity, however, focused on the nuclear-genome-encoded proteinsprimarily because of the lack of adequate mitochondrial-genome mutant mice. To study the role of mitochondrial-genome encoded proteins in autoimmunity a series of mitochondrial mutant mice (conplastic strains) have been recently generated in our group. In addition, by using this conplastic strains our group has previously reported the mtDNA mutations clearly associated with disease susceptibility in a series of experimental autoimmune models (Yu et al Genome Res 2009). This motivated to study the role of mtDNA in autoimmune blistering skin diseases.The aim of this study is to investigate the potential role of mtDNA variations in the susceptibility to experimental autoimmune skin blistering diseases, in particularly epidermolysis bullosa acquisita (EBA). First, the screening of a panel of conplastic strains will be performed by inducing local EBA model. Once strains showing different disease susceptibility are identified, the responsible cell type (e.g. macrophages) will be sought, followed by functional study of such cells. Finally, the pathway mediating the mtDNA mutation and the downstream effect on the disease will be elucidated.

Paul graduated in March 2017. Congratulations!