title: Type I interferon and Toll-like receptor expression characterizes inflammatory myopathies.
abstract: OBJECTIVE
  Juvenile dermatomyositis (JDM), adult dermatomyositis, and polymyositis (PM) are idiopathic inflammatory myopathies (IIMs) characterized by muscle infiltration and specific muscle fiber alterations. They are thought to have an autoimmune etiology, but triggering factors, and how immunologic attack induces muscle weakness, remain unknown. Recent evidence suggests a key role for type I interferon (IFN)-mediated innate immunity in dermatomyositis, which we explored in JDM, dermatomyositis, and PM by gene expression profiling, and other methods.
  
  
  METHODS
  Ten IIM and 5 control muscle biopsies were assessed for expression of approximately 16,000 genes by microarray; 37 additional IIM, 10 dystrophinopathic, and 14 nonmyopathic control muscles were studied for type I IFN-dependent genes, and Toll-like receptor (TLR) expression by immunochemistry and PCR.
  
  
  RESULTS
  Type I IFN-dependent transcripts were significantly upregulated in IIM muscles compared to controls; in JDM the most expressed were ISG15 (408-fold), IFIT3 (261-fold), MX1 (99-fold), and IRF7 (37-fold). IFN-β (but not IFN-α) transcripts were upregulated in PM as well as dermatomyositis/JDM. TLR3 was upregulated particularly in JDM, being localized on vascular endothelial cells, muscle infiltrating cells (mainly myeloid dendritic cells), and regenerating myofibers; TLR7 and TLR9 proteins were present in IIM (prominently in PM), mainly on cell infiltrates, particularly plasma cells, and on some injured myofibers.
  
  
  CONCLUSIONS
  IFN-β and type I IFN-induced molecules are involved in PM as well as JDM/dermatomyositis. Endosomal TLRs (effectors of innate immunity) are also involved (but differently) in the 3 conditions, further suggesting viral involvement, although TLR activation could be secondary to tissue damage.
authors.affiliation: Department of Neurology IV, Neurological Institute Foundation Carlo Besta, Via Celoria 11, 20133 Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Cappelletti
authors.forename: F
authors.initials: F
authors.lastname: Baggi
authors.forename: F
authors.initials: F
authors.lastname: Zolezzi
authors.forename: D
authors.initials: D
authors.lastname: Biancolini
authors.forename: O
authors.initials: O
authors.lastname: Beretta
authors.forename: M
authors.initials: M
authors.lastname: Severa
authors.forename: E M
authors.initials: EM
authors.lastname: Coccia
authors.forename: P
authors.initials: P
authors.lastname: Confalonieri
authors.forename: L
authors.initials: L
authors.lastname: Morandi
authors.forename: M
authors.initials: M
authors.lastname: Mora
authors.forename: R
authors.initials: R
authors.lastname: Mantegazza
authors.forename: P
authors.initials: P
authors.lastname: Bernasconi
mesh_terms: D003882:Dermatomyositis / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D046228:Microarray Analysis; D018482:Muscle, Skeletal / Q000166:cytology / Q000276:immunology / Q000473:pathology / Q000502:physiology; D009220:Myositis / Q000235:genetics / Q000276:immunology*; D017285:Polymyositis / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D051193:Toll-Like Receptors