Absence of T and B lymphocytes modulates dystrophic features in dysferlin deficient animal model

Abstract

Dysferlin mutations cause muscular dystrophy (dysferlinopathy) characterized by adult onset muscle weakness, high serum creatine kinase levels, attenuation of muscle regeneration and a prominent inflammatory infiltrate. In order to verify the role of lymphocytes and immune cells on this disease, we generated the Scid/A/J transgenic mice and compared these animals with the age-matched A/J mice. The absence of T and B lymphocytes in this animal model of dysferlinopathy resulted in an improvement of the muscle regeneration. Scid/A/J mice showed increased specific force in the myosin heavy chain 2A-expressing fibers of the diaphragm and abdominal muscles. Moreover, a partial reduction in complement deposition was observed together with a diminution in pro-inflammatory M1 macrophages. Consistent with this model, T and B lymphocytes seem to have a role in the muscle damaging immune response. The knowledge of the involvement of immune system in the development of dysferlinopathies could represent an important tool for their rescuing. By studying Scid/blAJ mice, we showed that it could be possible to modulate the pathological symptoms of these diseases by interfering with different components of the immune system.