title: 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-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.
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. avillalta@diabetes.ucsf.edu.
authors.forename: S Armando
authors.initials: SA
authors.lastname: Villalta
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Rosenthal
authors.affiliation: Department of Neurology and Center for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Leonel
authors.initials: L
authors.lastname: Martinez
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Amanjot
authors.initials: A
authors.lastname: Kaur
authors.affiliation: Institute for Infection Immunology, Twincore, Hannover 30625, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Molecular, Cellular, and Integrative Physiology Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Tidball
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Margeta
authors.affiliation: Department of Neurology and Center for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Spencer
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA. Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000276:immunology* / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000276:immunology* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma