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Paper Readig Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy  S. Armando Villalta1,*, Wendy Rosenthal1, Leonel Martinez2, Amanjot Kaur1,Tim Sparwasser3, James G. Tidball4, Marta Margeta5, Melissa J. Spencer2, and Jeffrey A. Bluestone1,6 Sci Transl Med. 2014 Duchenne muscular dystrophy (DMD) is a lethal muscle degenerative disorder that is caused by loss-of-function mutations in the dystrophin gene. DMD is characterized by a progressive deterioration of muscle function and strength, loss of ambulation by the second decade of life and death in the early to mid-20s. Although the lack of dystrophin protein is the primary defect responsible for the development of muscular dystrophy, secondary disease processes such as muscle inflammation contribute greatly to the pathogenesis of DMD. The leukocyte infiltrate of dystrophic muscle is heterogeneous comprising neutrophils, eosinophils, macrophages, and CD8+ and CD4+ T cells. Regulatory T cells (Tregs) are candidate immunosuppressive lymphocytes that possess the functional capacity to modulate dystrophinopathy by regulating the balance between type 1 and type 2 inflammatory responses. Previous studies have reported that Tregs accumulate in dystrophic muscle and have shown that FoxP3 mRNA is increased in muscle from osteopontin-deficient mdx mice, suggesting that their numbers or stability are partly regulated by osteopontin. In this paper, they also found that Tregs are elevated in human DMD/BMD and mouse mdx muscle and display an activated phenotype. And depletion of Tregs revealed an increase in immune cell infiltration and an enhanced type 1 inflammatory response, which resulted in exacerbated myofiber damage. Collectively, these findings show that Tregs play a critical role in limiting muscle damage during muscular dystrophy by suppressing the development of type 1 inflammatory responses, and demonstrate the potential clinical value of therapeutically targeting Tregs in DMD. doi:10.1126/scitranslmed.3009925. Poor Repair of Skeletal Muscle in Aging Mice Reflects a Defect in Local, Interleukin-33-Dependent Accumulation of Regulatory T Cells  Wilson Kuswanto, Dalia Burzyn, Marisella Panduro, ..., Amy J. Wagers, Christophe Benoist, Diane Mathis Immunity. 2016 Foxp3+CD4+ regulatory T (Treg) cells play a key role in immune-system homeostasis. In visceral-adipose-tissue (VAT) and skeletal muscle, Treg cells can exert a direct influence on local parenchymal cells or their progenitors, in addition to regulating macrophage activities. Skeletal muscle is a highly specialized tissue composed largely of post-mitotic, multinucleate cells (myofibers) that rarely turn over in the absence of damage. Upon injury, muscle mounts a robust regenerative response that supports repair or replacement of almost all of the neighboring myofibers. Muscle regeneration is dependent on a pool of quiescent, committed, self-renewable precursors, called satellite cells, found beneath the basal lamina in juxtaposition to muscle fibers. Muscle Treg cells display a distinct, clonally expanded, T cell receptor (TCR) repertoire that shows signs of antigenic selection. The muscle Treg cell transcriptome, although enriched for signature transcripts, differs substantially from those of Treg cells found in lymphoid tissues. Aging of skeletal muscle, like that of most mammalian tissues, is associated with a steady decline in both function and regenerative capacity. In this paper, they found that Treg cell accumulation diminished in skeletal muscle and Treg cell recruitment, proliferation, and retention defected in aged mice. More importantly, Exogenous Addition of IL-33 Restores the Treg Cell Population in Injured Muscle of Aged Mice, Enhancing Regeneration. Age-related sarcopenia and associated defects in muscle repair subsequent to injury or atrophy represent a major health problem with our aging population structure, exerting a strong impact on mobility, independence, and quality of life. The IL-33: ST2 axis seems to be a promising avenue to explore in attempts to address this important problem. http://dx./10.1016/j.immuni.2016.01.009 Edited by Biaolong Deng  |
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