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Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy.
Villalta, S Armando Rosenthal, Wendy Martinez, Leonel Kaur, Amanjot Sparwasser, Tim Tidball, James G Margeta, Marta Spencer, Melissa J Bluestone, Jeffrey A
Villalta, S Armando
Rosenthal, Wendy
Martinez, Leonel
Kaur, Amanjot
Sparwasser, Tim
Tidball, James G
Margeta, Marta
Spencer, Melissa J
Bluestone, Jeffrey A
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2014-10-15
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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-γ (IFN-γ) 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.
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Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy. 2014, 6 (258):258ra142 Sci Transl Med
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en
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1946-6242