Systematic analysis of immune cell populations in muscles and tissues throughout the lifespan of dysferlin-deficient BLAJ mice
Dysferlinopathies are strongly associated with infiltration of immune cells and inflammation, likely driven by impaired membrane function and increasing levels of damage-associated molecular patterns. However, it is not clear whether factors associated with the myofibres or an altered microenvironment may directly activate the immune response, compared with the extent that altered dysferlin-deficient immune cells may exacerbate and distort the immune response. There are clinically approved drugs that target dysregulated immune function, that are potentially suitable for dysferlinopathies, but first we need to identify the specific nature of the immune dysregulation to determine the best targets for therapy. Therefore, the aim of this project is to thoroughly investigate differences in key immune cell populations from many tissues of dysferlin deficient BLA/J compared with control wild-type C57BL/6J mice, in the context of both age and sex, throughout their lifespan. Understanding the cellular changes related to the immune response will help to establish the impact of inflammatory dysfunction in dysferlinopathies. This new insight will also help inform decisions for selecting appropriate candidate drugs for therapy and potentially identify immune-related biomarkers of dysferlinopathic changes.