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Immune System Regulation of Muscle Injury and Disease

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Muscle Gene Therapy

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Abstract

Muscular dystrophy and inflammatory myopathy are muscle diseases that despite their etiological differences share many pathological features, including muscle degeneration, loss of function, and chronic inflammation. Immunological processes induced by muscle injury contribute to the pathology of various muscular dystrophies, whereas autoimmune responses specific for yet undefined muscle antigens are suspected to be the cause of some idiopathic inflammatory myopathies. This chapter discusses the role of the immune system in eliciting immunity and regulating inflammatory responses during acute injury and muscle degenerative diseases. Duchenne muscular dystrophy (DMD) is the most prevalent form of muscular dystrophy. Using DMD as an example, we discuss the role of immune system in the pathogenesis of muscle disease. In addition to the role of innate immunity, we review the literature supporting the elicitation of antigen-specific, adaptive immune responses in DMD, including those specific for dystrophin. We discuss the clinical implications of these adaptive immune responses and their potential in limiting the efficacy of dystrophin gene therapy. Last, we highlight therapeutic approaches that may be used to inhibit degenerative muscle inflammation and to tolerize DMD patients to the protein product of dystrophin gene therapy.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, USA

    Jenna M. Kastenschmidt & S. Armando Villalta

  2. Institute for Immunology, University of California Irvine, Irvine, CA, USA

    Jenna M. Kastenschmidt, Ali H. Mannaa, Karissa J. Muñoz & S. Armando Villalta

Authors
  1. Jenna M. Kastenschmidt
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  2. Ali H. Mannaa
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  3. Karissa J. Muñoz
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  4. S. Armando Villalta
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Correspondence to S. Armando Villalta .

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Editors and Affiliations

  1. Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USA; Department of Neurology, School of Medicine, University of Missouri, Columbia, MO, USA, Department of Biomedical Sciences College of Veterinary Medicine, University of Missouri, Columbia, MO, USA; Department of Bioengineering, University of Missouri, Columbia, MO, USA

    Dongsheng Duan

  2. Department of Pediatrics Nationwide Children’s Hospital and Research Institute, Department of Neurology Nationwide Children’s Hospital and Research Institute, The Ohio State University, Columbus, OH, USA

    Jerry R. Mendell

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Kastenschmidt, J.M., Mannaa, A.H., Muñoz, K.J., Villalta, S.A. (2019). Immune System Regulation of Muscle Injury and Disease. In: Duan, D., Mendell, J. (eds) Muscle Gene Therapy. Springer, Cham. https://doi.org/10.1007/978-3-030-03095-7_7

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