Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy

We examined the hypothesis that regulatory T cells (T-regs) modulate muscle injury and inflammation in the mdx mouse model of Duchenne muscular dystrophy (DMD). Although T-regs were largely absent in the muscle of wild-type mice and normal human muscle, they were present in necrotic lesions, displayed an activated phenotype, and showed increased expression of interleukin-10 (IL-10) in dystrophic muscle from mdx mice. Depletion of T-regs exacerbated muscle injury and the severity of muscle inflammation, which was characterized by an enhanced interferon-gamma (IFN-gamma) response and activation of M1 macrophages. To test the therapeutic value of targeting T-regs in muscular dystrophy, we treated mdx mice with IL-2/anti-IL-2 complexes and found that T-regs and IL-10 concentrations were increased in muscle, resulting in reduced expression of cyclooxygenase-2 and decreased my injury. These findings suggest that T-regs modulate the progression of muscular dystrophy by suppressing type 1 inflammation in muscle associated with muscle fiber injury, and highlight the potential of T-reg-modulating agents as therapeutics for DMD.