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Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy.


ABSTRACT: We examined the hypothesis that regulatory T cells (Tregs) modulate muscle injury and inflammation in the mdx mouse model of Duchenne muscular dystrophy (DMD). Although Tregs 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 Tregs exacerbated muscle injury and the severity of muscle inflammation, which was characterized by an enhanced interferon-? (IFN-?) response and activation of M1 macrophages. To test the therapeutic value of targeting Tregs in muscular dystrophy, we treated mdx mice with IL-2/anti-IL-2 complexes and found that Tregs and IL-10 concentrations were increased in muscle, resulting in reduced expression of cyclooxygenase-2 and decreased myofiber injury. These findings suggest that Tregs modulate the progression of muscular dystrophy by suppressing type 1 inflammation in muscle associated with muscle fiber injury, and highlight the potential of Treg-modulating agents as therapeutics for DMD.

SUBMITTER: Villalta SA 

PROVIDER: S-EPMC4889432 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy.

Villalta S Armando SA   Rosenthal Wendy W   Martinez Leonel L   Kaur Amanjot A   Sparwasser Tim T   Tidball James G JG   Margeta Marta M   Spencer Melissa J MJ   Bluestone Jeffrey A JA  

Science translational medicine 20141001 258


We examined the hypothesis that regulatory T cells (Tregs) modulate muscle injury and inflammation in the mdx mouse model of Duchenne muscular dystrophy (DMD). Although Tregs 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 Tregs exacerbated muscle injury and the severity of muscle inflammat  ...[more]

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