Inflammation in a severe model of dystrophic cardiomyopathy contains a high proportion of T cells that contribute to onset of pathology.

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder with progressive muscle degeneration and cardiomyopathy leading to heart failure. The inflammatory environment in dystrophic skeletal muscle is well-studied, but little is known about inflammation in DMD cardiomyopathy due to the lack of adequate animal models. We recently developed the Fiona/dko mouse model, deficient for both dystrophin and utrophin, but containing a skeletal muscle-specific expressing utrophin transgene allowing progression of dystrophic cardiomyopathy. This Fiona/dko model is the first DMD cardiomyopathy model to reproducibly progress to reduced cardiac contractile function by 9 mo. In this study, we compared immune cell composition between Fiona/dko mice and their milder littermates that develop cardiac pathology, but do not demonstrate whole heart dysfunction. Flow cytometry analysis revealed that T cells constitute a significant proportion of the immune cell population in dystrophic hearts, in contrast to the known predominantly myeloid signature in dystrophic skeletal muscles. T cell infiltration precedes the development of cardiac fibrosis and dysfunction in Fiona/dko mice. RNA sequencing of whole hearts after cardiac dysfunction shows increased expression of 68 genes related to T cell signaling in Fiona/dko compared with their milder littermates. Furthermore, depletion of circulating CD3