Advertisement

Immune System Regulation of Muscle Injury and Disease

  • Jenna M. Kastenschmidt
  • Ali H. Mannaa
  • Karissa J. Muñoz
  • S. Armando VillaltaEmail author
Chapter

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.

Keywords

Muscle immunology Inflammation Muscular dystrophy Gene therapy Muscle regeneration Macrophages T cells Regulatory T cells Dystrophin immunity Inflammatory myopathy Acute muscle injury 

References

  1. 1.
    Shackelford LC (2008) Musculoskeletal response to space flight. In: Principles of clinical medicine for space flight, pp 293–306.  https://doi.org/10.1007/978-0-387-68164-1_14 CrossRefGoogle Scholar
  2. 2.
    Jarvinen TAH (2005) Muscle injuries: biology and treatment. Am J Sports Med 33:745–764.  https://doi.org/10.1177/0363546505274714 CrossRefPubMedGoogle Scholar
  3. 3.
    Page P (1995) Pathophysiology of acute exercise-induced muscular injury: clinical implications. J Athl Train 30:29–34PubMedPubMedCentralGoogle Scholar
  4. 4.
    Mann CJ, Perdiguero E, Kharraz Y et al (2011) Aberrant repair and fibrosis development in skeletal muscle. Skelet Muscle 1:21.  https://doi.org/10.1186/2044-5040-1-21 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Rayavarapu S, Coley W, Kinder TB, Nagaraju K (2013) Idiopathic inflammatory myopathies: pathogenic mechanisms of muscle weakness. Skelet Muscle 3:13.  https://doi.org/10.1186/2044-5040-3-13 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Lu H, Huang D, Ransohoff RM, Zhou L (2011) Acute skeletal muscle injury: CCL2 expression by both monocytes and injured muscle is required for repair. FASEB J 25:3344–3355.  https://doi.org/10.1096/fj.10-178939 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Nguyen HX, Tidball JG (2003) Null mutation of gp91phox reduces muscle membrane lysis during muscle inflammation in mice. J Physiol 553:833–841.  https://doi.org/10.1113/jphysiol.2003.051912 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Pizza FX, Peterson JM, Baas JH, Koh TJ (2005) Neutrophils contribute to muscle injury and impair its resolution after lengthening contractions in mice. J Physiol 562:899–913.  https://doi.org/10.1113/jphysiol.2004.073965 CrossRefPubMedGoogle Scholar
  9. 9.
    Swirski FK, Nahrendorf M, Etzrodt M et al (2010) Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325:612–616.  https://doi.org/10.1126/science.1175202.Identification CrossRefGoogle Scholar
  10. 10.
    Tidball JG (2005) Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol 288:345–353.  https://doi.org/10.1152/ajpregu.00454.2004 CrossRefGoogle Scholar
  11. 11.
    Arnold L, Henry A, Poron F et al (2007) Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med 204:1057–1069.  https://doi.org/10.1084/jem.20070075 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Nguyen HX, Tidball JG (2002) Interactions between neutrophils and macrophages promote macrophage killing of rat muscle cells in vitro. J Physiol 547:125–132.  https://doi.org/10.1113/jphysiol.2002.031450 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122:787–795.  https://doi.org/10.1172/JCI59643DS1 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Burzyn D, Kuswanto W, Kolodin D et al (2013) A special population of regulatory T cells potentiates muscle repair. Cell 155:1282–1295.  https://doi.org/10.1016/j.cell.2013.10.054 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Deng B, Wehling-Henricks M, Villalta SA et al (2012) IL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration. J Immunol 189:3669–3680.  https://doi.org/10.4049/jimmunol.1103180 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Tidball JG, Wehling-Henricks M (2007) Macrophages promote muscle membrane repair and muscle fibre growth and regeneration during modified muscle loading in mice in vivo. J Physiol 578:327–336.  https://doi.org/10.1113/jphysiol.2006.118265 CrossRefPubMedGoogle Scholar
  17. 17.
    Mounier RM, Théret M, Arnold L et al (2013) AMPKα1 regulates macrophage skewing at the time of resolution of inflammation during skeletal muscle regeneration. Cell Metab 18:251–264.  https://doi.org/10.1016/j.cmet.2013.06.017 CrossRefPubMedGoogle Scholar
  18. 18.
    Hammers DW, Rybalko V, Merscham-Banda M et al (2015) Anti-inflammatory macrophages improve skeletal muscle recovery from ischemia-reperfusion. J Appl Physiol 118:1067–1074.  https://doi.org/10.1152/japplphysiol.00313.2014 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Martinez FO, Helming L, Gordon S (2009) Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 27:451–483.  https://doi.org/10.1146/annurev.immunol.021908.132532 CrossRefPubMedGoogle Scholar
  20. 20.
    Varga T, Mounier RM, Patsalos A et al (2016) Macrophage PPARγ, a lipid activated transcription factor controls the growth factor GDF3 and skeletal muscle regeneration. Immunity 45:1038–1051.  https://doi.org/10.1016/j.immuni.2016.10.016 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Musarò A, Giacinti C, Borsellino G et al (2004) Stem cell-mediated muscle regeneration is enhanced by local isoform of insulin-like growth factor 1. Proc Natl Acad Sci 101:1206–1210.  https://doi.org/10.1073/pnas.0303792101 CrossRefPubMedGoogle Scholar
  22. 22.
    Tonkin J, Temmerman L, Sampson RD et al (2016) Monocyte/macrophage-derived IGF-1 orchestrates murine skeletal muscle regeneration and modulates autocrine polarization. Mol Ther 23:1189–1200.  https://doi.org/10.1038/mt.2015.66 CrossRefGoogle Scholar
  23. 23.
    Lu H, Huang D, Saederup N et al (2011) Macrophages recruited via CCR2 produce insulin-like growth factor-1 to repair acute skeletal muscle injury. FASEB J 25:358–369.  https://doi.org/10.1096/fj.10-171579 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Brigitte M, Schilte C, Plonquet A et al (2010) Muscle resident macrophages control the immune cell reaction in a mouse model of notexin-induced myoinjury. Arthritis Rheum 62:268–279.  https://doi.org/10.1002/art.27183 CrossRefPubMedGoogle Scholar
  25. 25.
    Zhao W, Lu H, Wang X et al (2016) CX3CR1 deficiency delays acute skeletal muscle injury repair by impairing macrophage functions. FASEB J 30:380–393.  https://doi.org/10.1096/fj.14-270090 CrossRefPubMedGoogle Scholar
  26. 26.
    Kohno S, Ueji T, Abe T et al (2011) Rantes secreted from macrophages disturbs skeletal muscle regeneration after cardiotoxin injection in Cbl-b-deficient mice. Muscle Nerve 43:223–229.  https://doi.org/10.1002/mus.21829 CrossRefPubMedGoogle Scholar
  27. 27.
    Alam R, Stafford S, Forsythe P et al (1993) RANTES is a chemotactic and activating factor for human eosinophils. J Immunol 150:3442–3448PubMedGoogle Scholar
  28. 28.
    Heredia JE, Mukundan L, Chen FM et al (2013) Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration. Cell 153:376–388.  https://doi.org/10.1016/j.cell.2013.02.053 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Castiglioni A, Corna G, Rigamonti E et al (2015) FOXP3+ T cells recruited to sites of sterile skeletal muscle injury regulate the fate of satellite cells and guide effective tissue regeneration. PLoS One 10:1–18.  https://doi.org/10.1371/journal.pone.0128094 CrossRefGoogle Scholar
  30. 30.
    Koenig M, Hoffman EP, Bertelson CJ et al (1987) Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50:509–517CrossRefGoogle Scholar
  31. 31.
    Hoffman EP, Brown RHJ, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919–928CrossRefGoogle Scholar
  32. 32.
    Moat SJ, Bradley DM, Salmon R et al (2013) Newborn bloodspot screening for Duchenne muscular dystrophy: 21 years experience in Wales (UK). Eur J Hum Genet 21:1049–1053.  https://doi.org/10.1038/ejhg.2012.301 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Mendell JR, Shilling C, Leslie ND et al (2012) Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann Neurol 71:304–313.  https://doi.org/10.1002/ana.23528 CrossRefPubMedGoogle Scholar
  34. 34.
    Petrof BJ, Shrager JB, Stedman HH et al (1993) Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci U S A 90:3710–3714CrossRefGoogle Scholar
  35. 35.
    Spencer MJ, Tidball JG (2001) Do immune cells promote the pathology of dystrophin-deficient myopathies? Neuromuscul Disord 11:556–564CrossRefGoogle Scholar
  36. 36.
    Dadgar S, Wang Z, Johnston H et al (2014) Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy. J Cell Biol 207:139–158.  https://doi.org/10.1083/jcb.201402079 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lundberg I, Brengman JM, Engel AG (1995) Analysis of cytokine expression in muscle in inflammatory myopathies, Duchenne dystrophy, and non-weak controls. J Neuroimmunol 63:9–16CrossRefGoogle Scholar
  38. 38.
    Haslett JN, Sanoudou D, Kho AT et al (2002) Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. Proc Natl Acad Sci U S A 99:15000–15005CrossRefGoogle Scholar
  39. 39.
    McDouall RM, Dunn MJ, Dubowitz V (1990) Nature of the mononuclear infiltrate and the mechanism of muscle damage in juvenile dermatomyositis and Duchenne muscular dystrophy. J Neurol Sci 99:199–217CrossRefGoogle Scholar
  40. 40.
    Pescatori M, Broccolini A, Minetti C et al (2007) Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression. FASEB J 21:1210–1226CrossRefGoogle Scholar
  41. 41.
    Coutinho AE, Chapman KE (2011) The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 335:2–13.  https://doi.org/10.1016/j.mce.2010.04.005 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Schakman O, Kalista S, Barbé C et al (2013) Glucocorticoid-induced skeletal muscle atrophy. Int J Biochem Cell Biol 45:2163–2172.  https://doi.org/10.1016/j.biocel.2013.05.036 CrossRefPubMedGoogle Scholar
  43. 43.
    Wehling-Henricks M, Lee JJ, Tidball JG (2004) Prednisolone decreases cellular adhesion molecules required for inflammatory cell infiltration in dystrophin-deficient skeletal muscle. Neuromuscul Disord 14:483–490CrossRefGoogle Scholar
  44. 44.
    Cai B, Spencer MJ, Nakamura G et al (2000) Eosinophilia of dystrophin-deficient muscle is promoted by perforin-mediated cytotoxicity by T cell effectors. Am J Pathol 156:1789–1796CrossRefGoogle Scholar
  45. 45.
    Spencer MJ, Montecino-Rodriguez E, Dorshkind K, Tidball JG (2001) Helper (CD4(+)) and cytotoxic (CD8(+)) T cells promote the pathology of dystrophin-deficient muscle. Clin Immunol 98:235–243CrossRefGoogle Scholar
  46. 46.
    Wehling M, Spencer MJ, Tidball JG (2001) A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice. J Cell Biol 155:123–131CrossRefGoogle Scholar
  47. 47.
    Madaro L, Bouche M (2014) From innate to adaptive immune response in muscular dystrophies and skeletal muscle regeneration: the role of lymphocytes. Biomed Res Int 2014:1–23.  https://doi.org/10.1155/2014/438675 CrossRefGoogle Scholar
  48. 48.
    De Paepe B, De Bleecker JL (2013) Cytokines and chemokines as regulators of skeletal muscle inflammation: presenting the case of Duchenne muscular dystrophy. Mediat Inflamm 2013:1–10.  https://doi.org/10.1155/2013/540370 CrossRefGoogle Scholar
  49. 49.
    Rosenberg AS, Puig M, Nagaraju K et al (2015) Immune-mediated pathology in Duchenne muscular dystrophy. Sci Transl Med 7:299rv4.  https://doi.org/10.1126/scitranslmed.aaa7322 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Tidball JG (2017) Regulation of muscle growth and regeneration by the immune system. Nat Publ Group 17:165–178.  https://doi.org/10.1038/nri.2016.150 CrossRefGoogle Scholar
  51. 51.
    Villalta SA, Rosenberg AS, Bluestone JA (2015) The immune system in Duchenne muscular dystrophy: friend or foe. Rare Dis 3:e1010966.  https://doi.org/10.1080/21675511.2015.1010966 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Gordon S (2003) Alternative activation of macrophages. Nat Rev Immunol 3:23–35CrossRefGoogle Scholar
  53. 53.
    Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969CrossRefGoogle Scholar
  54. 54.
    Villalta SA, Nguyen HX, Deng B et al (2009) Shifts in macrophage phenotypes and macrophage competition for arginine metabolism affect the severity of muscle pathology in muscular dystrophy. Hum Mol Genet 18:482–496CrossRefGoogle Scholar
  55. 55.
    Yang-Snyder JA, Rothenberg EV (1998) Spontaneous expression of interleukin-2 in vivo in specific tissues of young mice. Dev Immunol 5:223–245.  https://doi.org/10.1155/1998/12421 CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Malek TR (2008) The biology of interleukin-2. Annu Rev Immunol 26:453–479.  https://doi.org/10.1146/annurev.immunol.26.021607.090357 CrossRefPubMedGoogle Scholar
  57. 57.
    Granucci F, Vizzardelli C, Pavelka N et al (2001) Inducible IL-2 production by dendritic cells revealed by global gene expression analysis. Nat Immunol 2:882–888.  https://doi.org/10.1038/ni0901-882 CrossRefPubMedGoogle Scholar
  58. 58.
    Burchill MA, Yang J, Vogtenhuber C et al (2007) IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J Immunol 178:280–290CrossRefGoogle Scholar
  59. 59.
    Klatzmann D, Abbas AK (2015) The promise of low-dose interleukin-2 therapy for autoimmune and inflammatory diseases. Nat Rev Immunol 15:283–294.  https://doi.org/10.1038/nri3823 CrossRefPubMedGoogle Scholar
  60. 60.
    Villalta SA, Rosenthal W, Martinez L et al (2014) Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy. Sci Transl Med 6:258ra142.  https://doi.org/10.1126/scitranslmed.3009925 CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Vercoulen Y, Enders FB, Meerding J et al (2014) Increased presence of FOXP3+ regulatory T cells in inflamed muscle of patients with active juvenile dermatomyositis compared to peripheral blood. PLoS One 9:e105353.  https://doi.org/10.1371/journal.pone.0105353 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Antiga E, Kretz CC, Klembt R et al (2010) Characterization of regulatory T cells in patients with dermatomyositis. J Autoimmun 35:342–350.  https://doi.org/10.1016/j.jaut.2010.07.006 CrossRefPubMedGoogle Scholar
  63. 63.
    Vetrone SA, Montecino-Rodriguez E, Kudryashova E et al (2009) Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-beta. J Clin Invest 119:1583–1594CrossRefGoogle Scholar
  64. 64.
    Tiemessen MM, Jagger AL, Evans HG et al (2007) CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc Natl Acad Sci U S A 104:19446–19451CrossRefGoogle Scholar
  65. 65.
    Villalta SA, Rinaldi C, Deng B et al (2011) Interleukin-10 reduces the pathology of mdx muscular dystrophy by deactivating M1 macrophages and modulating macrophage phenotype. Hum Mol Genet 20:790–805CrossRefGoogle Scholar
  66. 66.
    Nitahara-Kasahara Y, Hayashita-Kinoh H, Chiyo T et al (2014) Dystrophic mdx mice develop severe cardiac and respiratory dysfunction following genetic ablation of the anti-inflammatory cytokine IL-10. Hum Mol Genet 23:3990–4000.  https://doi.org/10.1093/hmg/ddu113 CrossRefPubMedGoogle Scholar
  67. 67.
    Tang Q, Bluestone JA (2008) The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol 9:239–244CrossRefGoogle Scholar
  68. 68.
    Vignali DA, Collison LW, Workman CJ (2008) How regulatory T cells work. Nat Rev Immunol 8:523–532CrossRefGoogle Scholar
  69. 69.
    Iwasaki A, Medzhitov R (2015) Control of adaptive immunity by the innate immune system. Nat Immunol 16:343–353.  https://doi.org/10.1038/ni.3123 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Lagrota-Candido J, Vasconcellos R, Cavalcanti M et al (2002) Resolution of skeletal muscle inflammation in mdx dystrophic mouse is accompanied by increased immunoglobulin and interferon-γ production. Int J Exp Pathol 83:121–132.  https://doi.org/10.1046/j.1365-2613.2002.00221.x CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Farini A, Sitzia C, Cassani B et al (2016) Therapeutic potential of immunoproteasome inhibition in Duchenne muscular dystrophy. Mol Ther 24:1898–1912.  https://doi.org/10.1038/mt.2016.162 CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Ferraccioli G, Tolusso B (2007) Infections, B cell receptor activation and autoimmunity: different check-point impairments lead to autoimmunity, clonal B cell expansion and fibrosis in different immunological settings. Autoimmun Rev 7:109–113.  https://doi.org/10.1016/j.autrev.2007.02.013 CrossRefPubMedGoogle Scholar
  73. 73.
    Denizot F, Wilson A, Battye F et al (1986) Clonal expansion of T cells: a cytotoxic T-cell response in vivo that involves precursor cell proliferation. Proc Natl Acad Sci 83:6089–6092CrossRefGoogle Scholar
  74. 74.
    Gussoni E, Pavlath GK, Miller RG et al (1994) Specific T cell receptor gene rearrangements at the site of muscle degeneration in Duchenne muscular dystrophy. J Immunol 153:4798–4805PubMedGoogle Scholar
  75. 75.
    Eghtesad S, Zheng H, Nakai H et al (2010) Effects of irradiating adult mdx mice before full-length dystrophin cDNA transfer on host anti-dystrophin immunity. Gene Ther 17:1181–1190.  https://doi.org/10.1038/gt.2010.108 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Flanigan KM, Campbell K, Viollet L et al (2013) Anti-dystrophin T cell responses in Duchenne muscular dystrophy: prevalence and a glucocorticoid treatment effect. Hum Gene Ther 24:797.  https://doi.org/10.1089/hgtb.2013.092 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Mendell JR, Campbell K, Rodino-Klapac L et al (2010) Dystrophin immunity in Duchenne’s muscular dystrophy. N Engl J Med 363:1429–1437CrossRefGoogle Scholar
  78. 78.
    Arahata K, Engel AG (1988) Monoclonal antibody analysis of mononuclear cells in myopathies. IV: cell-mediated cytotoxicity and muscle fiber necrosis. Ann Neurol 23:168–173CrossRefGoogle Scholar
  79. 79.
    Arahata K, Engel AG (1984) Monoclonal antibody analysis of mononuclear cells in myopathies. I: quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells. Ann Neurol 16:193–208.  https://doi.org/10.1002/ana.410160206 CrossRefPubMedGoogle Scholar
  80. 80.
    Spencer MJ, Walsh CM, Dorshkind KA et al (1997) Myonuclear apoptosis in dystrophic mdx muscle occurs by perforin-mediated cytotoxicity. J Clin Invest 99:2745–2751CrossRefGoogle Scholar
  81. 81.
    Allenbach Y, Chaara W, Rosenzwajg M et al (2014) Th1 response and systemic Treg deficiency in inclusion body myositis. PLoS One 9:e88788.  https://doi.org/10.1371/journal.pone.0088788 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Pandya JM, Fasth AER, Zong M et al (2010) Expanded T cell receptor Vβ-restricted T cells from patients with sporadic inclusion body myositis are proinflammatory and cytotoxic CD28null T cells. Arthritis Rheum 62:3457–3466.  https://doi.org/10.1002/art.27665 CrossRefPubMedGoogle Scholar
  83. 83.
    Strioga M, Pasukoniene V, Characiejus D (2011) CD8+ CD28- and CD8+ CD57+ T cells and their role in health and disease. Immunology 134:17–32.  https://doi.org/10.1111/j.1365-2567.2011.03470.x CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Greenberg SA, Pinkus JL, Amato AA et al (2016) Association of inclusion body myositis with T cell large granular lymphocytic leukaemia. Brain J Neurol 139:1348–1360.  https://doi.org/10.1093/brain/aww024 CrossRefGoogle Scholar
  85. 85.
    Suurmond J, Diamond B (2015) Autoantibodies in systemic autoimmune diseases: specificity and pathogenicity. J Clin Invest 125:2194–2202.  https://doi.org/10.1172/JCI78084 CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Larman HB, Salajegheh M, Nazareno R et al (2013) Cytosolic 5′-nucleotidase 1A autoimmunity in sporadic inclusion body myositis. Ann Neurol 73:408–418.  https://doi.org/10.1002/ana.23840 CrossRefPubMedGoogle Scholar
  87. 87.
    Goyal NA, Cash TM, Alam U et al (2016) Seropositivity for NT5c1A antibody in sporadic inclusion body myositis predicts more severe motor, bulbar and respiratory involvement. J Neurol Neurosurg Psychiatry 87:373–378.  https://doi.org/10.1136/jnnp-2014-310008 CrossRefPubMedGoogle Scholar
  88. 88.
    Lilleker JB, Rietveld A, Pye SR et al (2017) Cytosolic 5′-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis. Ann Rheum Dis 76:862–868.  https://doi.org/10.1136/annrheumdis-2016-210282 CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Frisullo G, Frusciante R, Nociti V et al (2011) CD8(+) T cells in facioscapulohumeral muscular dystrophy patients with inflammatory features at muscle MRI. J Clin Immunol 31:155–166.  https://doi.org/10.1007/s10875-010-9474-6 CrossRefPubMedGoogle Scholar
  90. 90.
    Raju R, Dalakas MC (2005) Gene expression profile in the muscles of patients with inflammatory myopathies: effect of therapy with IVIg and biological validation of clinically relevant genes. Brain 128:1887–1896.  https://doi.org/10.1093/brain/awh518 CrossRefPubMedGoogle Scholar
  91. 91.
    Raju R, Vasconcelos O, Granger R, Dalakas MC (2003) Expression of IFN-γ-inducible chemokines in inclusion body myositis. J Neuroimmunol 141:125–131.  https://doi.org/10.1016/S0165-5728(03)00218-2 CrossRefPubMedGoogle Scholar
  92. 92.
    Schmidt J, Barthel K, Wrede A et al (2008) Interrelation of inflammation and APP in sIBM: IL-1 beta induces accumulation of beta-amyloid in skeletal muscle. Brain 131:1228–1240CrossRefGoogle Scholar
  93. 93.
    Banica L, Besliu A, Pistol G et al (2009) Quantification and molecular characterization of regulatory T cells in connective tissue diseases. Autoimmunity 42:41–49.  https://doi.org/10.1080/08916930802282651 CrossRefPubMedGoogle Scholar
  94. 94.
    Chaudhry A, Samstein RM, Treuting P et al (2011) Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity 34:566–578.  https://doi.org/10.1016/j.immuni.2011.03.018 CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Wan YY, Flavell RA (2007) “Yin-Yang” functions of TGF-β and Tregs in immune regulation. Immunol Rev 220:199–213.  https://doi.org/10.1111/j.1600-065X.2007.00565.x CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Baldwin AS (2001) Series introduction: the transcription factor NF-kappaB and human disease. J Clin Invest 107:3–6.  https://doi.org/10.1172/JCI11891 CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Acharyya S, Villalta SA, Bakkar N et al (2007) Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J Clin Invest 117:889–901CrossRefGoogle Scholar
  98. 98.
    Sun CC, Li SJ, Yang CL et al (2015) Sulforaphane attenuates muscle inflammation in dystrophin-deficient mdx mice via NF-E2-related factor 2 (Nrf2)-mediated inhibition of NF-κB signaling pathway. J Biol Chem 290:17784–17795.  https://doi.org/10.1074/jbc.M115.655019 CrossRefPubMedGoogle Scholar
  99. 99.
    Heier CR, Damsker JM, Yu Q et al (2013) VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular dystrophy without side effects. EMBO Mol Med 5:1569–1585.  https://doi.org/10.1002/emmm.201302621 CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Oakley R, Cidlowski JA (2013) The biology of the glucocorticoid receptor: new signaling mechanism in health and disease. J Allergy Clin Inmunol 132:1033–1044.  https://doi.org/10.1016/j.jaci.2013.09.007.The CrossRefGoogle Scholar
  101. 101.
    Muñoz-Cánoves P, Scheele C, Pedersen BK, Serrano AL (2013) Interleukin-6 myokine signaling in skeletal muscle: a double-edged sword? FEBS J 280:4131–4148.  https://doi.org/10.1111/febs.12338 CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Collins RA, Grounds MD (2001) The role of tumor necrosis factor-alpha (TNF-alpha) in skeletal muscle regeneration. Studies in TNF-alpha(-/-) and TNF-alpha(-/-)/LT-alpha(-/-) mice. J Histochem Cytochem 49:989–1001.  https://doi.org/10.1177/002215540104900807 CrossRefPubMedGoogle Scholar
  103. 103.
    Piers AT, Lavin T, Radley-Crabb HG et al (2011) Blockade of TNF in vivo using cV1q antibody reduces contractile dysfunction of skeletal muscle in response to eccentric exercise in dystrophic mdx and normal mice. Neuromuscul Disord 21:132–141.  https://doi.org/10.1016/j.nmd.2010.09.013 CrossRefPubMedGoogle Scholar
  104. 104.
    Keating GM, Perry CM, Farrell RJ et al (2002) Infliximab: an updated review of its use in Crohn’s disease and rheumatoid arthritis. BioDrugs 16:111–148CrossRefGoogle Scholar
  105. 105.
    Hunter CA, Jones SA (2015) IL-6 as a keystone cytokine in health and disease. Nat Immunol 16:448–457.  https://doi.org/10.1038/ni.3153 CrossRefPubMedGoogle Scholar
  106. 106.
    Rose-John S (2012) Il-6 trans-signaling via the soluble IL-6 receptor: importance for the proinflammatory activities of IL-6. Int J Biol Sci 8:1237–1247.  https://doi.org/10.7150/ijbs.4989 CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Gabay C (2006) Interleukin-6 and chronic inflammation. Arthritis Res Ther 8(Suppl 2):S3.  https://doi.org/10.1186/ar1917 CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Mammen AL, Sartorelli V (2015) IL-6 blockade as a therapeutic approach for Duchenne muscular dystrophy. EBioMedicine 2:274–275.  https://doi.org/10.1016/j.ebiom.2015.03.018 CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Pelosi L, Berardinelli MG, De Pasquale L et al (2015) Functional and morphological improvement of dystrophic muscle by interleukin 6 receptor blockade. EBioMedicine 2:285–293.  https://doi.org/10.1016/j.ebiom.2015.02.014 CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Kostek MC, Nagaraju K, Pistilli E et al (2012) IL-6 signaling blockade increases inflammation but does not affect muscle function in the mdx mouse. BMC Musculoskelet Disord 13:106.  https://doi.org/10.1186/1471-2474-13-106 CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Gazzerro E, Baldassari S, Assereto S et al (2015) Enhancement of muscle T regulatory cells and improvement of muscular dystrophic process in mdx mice by blockade of extracellular ATP/P2X axis. Am J Pathol 185:3349–3360.  https://doi.org/10.1016/j.ajpath.2015.08.010 CrossRefPubMedGoogle Scholar
  112. 112.
    Eghtesad S, Jhunjhunwala S, Little SR, Clemens PR (2011) Rapamycin ameliorates dystrophic phenotype in mdx mouse skeletal muscle. Mol Med 17:917CrossRefGoogle Scholar
  113. 113.
    Bodine SC, Stitt TN, Gonzalez M et al (2001) Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3:1014–1019.  https://doi.org/10.1038/ncb1101-1014 CrossRefPubMedGoogle Scholar
  114. 114.
    Eghtesad S, Jhunjhunwala S, Little SR, Clemens PR (2012) Effect of rapamycin on immunity induced by vector-mediated dystrophin expression in mdx skeletal muscle. Sci Rep 2:399.  https://doi.org/10.1038/srep00399 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Jenna M. Kastenschmidt
    • 1
    • 2
  • Ali H. Mannaa
    • 2
  • Karissa J. Muñoz
    • 2
  • S. Armando Villalta
    • 1
    • 2
    Email author
  1. 1.Department of Physiology and BiophysicsUniversity of California IrvineIrvineUSA
  2. 2.Institute for ImmunologyUniversity of California IrvineIrvineUSA

Personalised recommendations