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- Title
Defective dystrophic thymus determines degenerative changes in skeletal muscle.
- Authors
Farini, Andrea; Sitzia, Clementina; Villa, Chiara; Cassani, Barbara; Tripodi, Luana; Legato, Mariella; Belicchi, Marzia; Bella, Pamela; Lonati, Caterina; Gatti, Stefano; Cerletti, Massimiliano; Torrente, Yvan
- Abstract
In Duchenne muscular dystrophy (DMD), sarcolemma fragility and myofiber necrosis produce cellular debris that attract inflammatory cells. Macrophages and T-lymphocytes infiltrate muscles in response to damage-associated molecular pattern signalling and the release of TNF-α, TGF-β and interleukins prevent skeletal muscle improvement from the inflammation. This immunological scenario was extended by the discovery of a specific response to muscle antigens and a role for regulatory T cells (Tregs) in muscle regeneration. Normally, autoimmunity is avoided by autoreactive T-lymphocyte deletion within thymus, while in the periphery Tregs monitor effector T-cells escaping from central regulatory control. Here, we report impairment of thymus architecture of mdx mice together with decreased expression of ghrelin, autophagy dysfunction and AIRE down-regulation. Transplantation of dystrophic thymus in recipient nude mice determine the up-regulation of inflammatory/fibrotic markers, marked metabolic breakdown that leads to muscle atrophy and loss of force. These results indicate that involution of dystrophic thymus exacerbates muscular dystrophy by altering central immune tolerance. Immune cells are known to aggravate the inflammatory impact of Duchene muscular dystrophy. Here, the authors describe impaired thymic development and suggest thymic involution in this model of disease is linked to disease acceleration due to impaired immunological tolerance.
- Subjects
THYMUS; MUSCULAR atrophy; SUPPRESSOR cells; DUCHENNE muscular dystrophy; MUSCULAR dystrophy; SKELETAL muscle; T cells; PHYSIOLOGICAL effects of acceleration
- Publication
Nature Communications, 2021, Vol 12, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-22305-x