title: An update on pathogenic mechanisms of inflammatory myopathies.
abstract: OBJECTIVE
  Our understanding of the pathogenesis of the inflammatory myopathies suggests an interplay between adaptive, innate immune, and nonimmune mechanisms in the damage and dysfunction that occur in myopathic muscle tissue. This review gives an update on the recent findings concerning some of these mechanisms and their relevance to disease diagnosis, prognosis, and therapy.
  
  
  RESULTS
  The presence of several additional immune cell types (CD-28 null T cells, regulatory T cells, plasmacytoid dendritic cells, plasma cells) and their roles in the various subsets of myositis are discussed. Likewise several new autoantibodies (e.g. 3-hydroxy-3 methylglutaryl-coenzyme-A reductase and melanoma differentiation-associated gene 5) and their association with disease phenotype are described. The review also discusses emerging evidence that cytokines (type 1 interferon) and Toll-like receptor signaling influence the local immune cell activation and response. The mechanisms involved in muscle degeneration are not clearly defined, but recent studies point to a role for nonimmune mechanisms such as endoplasmic reticulum stress and autophagy in skeletal muscle cell death and dysfunction in myositis.
  
  
  CONCLUSIONS
  The muscle microenvironment in inflammatory myopathy is complex. Multiple players such as adaptive and innate immune cells, cytokines, and chemokines as well as nonimmune mechanisms are involved. Understanding the nature of the relevant cell types and the molecular pathways underlying particular disease phenotypes should help to define therapeutic targets for myositis.
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, The George Washington University, Washington, District of Columbia, USA.
authors.forename: Sree
authors.initials: S
authors.lastname: Rayavarapu
authors.forename: William
authors.initials: W
authors.lastname: Coley
authors.forename: Kanneboyina
authors.initials: K
authors.lastname: Nagaraju
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D001324:Autoantigens; D001343:Autophagy; D005081:Exercise Therapy; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D009220:Myositis / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D015398:Signal Transduction / Q000276:immunology; D013312:Stress, Physiological; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D051193:Toll-Like Receptors