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

2.50
Hdl Handle:
http://hdl.handle.net/10033/346327
Title:
Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy.
Authors:
Villalta, S Armando; Rosenthal, Wendy; Martinez, Leonel; Kaur, Amanjot; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Tidball, James G; Margeta, Marta; Spencer, Melissa J; Bluestone, Jeffrey A
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.
Affiliation:
Institute for Infection Immunology, Twincore, Hannover 30625, Germany
Citation:
Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy. 2014, 6 (258):258ra142 Sci Transl Med
Journal:
Science translational medicine
Issue Date:
15-Oct-2014
URI:
http://hdl.handle.net/10033/346327
DOI:
10.1126/scitranslmed.3009925
PubMed ID:
25320234
Type:
Article
Language:
en
ISSN:
1946-6242
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorVillalta, S Armandoen
dc.contributor.authorRosenthal, Wendyen
dc.contributor.authorMartinez, Leonelen
dc.contributor.authorKaur, Amanjoten
dc.contributor.authorSparwasser, Timen
dc.contributor.authorTidball, James Gen
dc.contributor.authorMargeta, Martaen
dc.contributor.authorSpencer, Melissa Jen
dc.contributor.authorBluestone, Jeffrey Aen
dc.date.accessioned2015-03-09T10:19:45Zen
dc.date.available2015-03-09T10:19:45Zen
dc.date.issued2014-10-15en
dc.identifier.citationRegulatory T cells suppress muscle inflammation and injury in muscular dystrophy. 2014, 6 (258):258ra142 Sci Transl Meden
dc.identifier.issn1946-6242en
dc.identifier.pmid25320234en
dc.identifier.doi10.1126/scitranslmed.3009925en
dc.identifier.urihttp://hdl.handle.net/10033/346327en
dc.description.abstractWe 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.en
dc.language.isoenen
dc.titleRegulatory T cells suppress muscle inflammation and injury in muscular dystrophy.en
dc.typeArticleen
dc.contributor.departmentInstitute for Infection Immunology, Twincore, Hannover 30625, Germanyen
dc.identifier.journalScience translational medicineen

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