title: Immature muscle precursors are a source of interferon-β in myositis: role of Toll-like receptor 3 activation and contribution to HLA class I up-regulation.
abstract: OBJECTIVE
  To investigate the production of type I interferon (IFN) by myoblasts and to identify its cell source and the link to Toll-like receptor (TLR) and C-type lectin receptor (CLR) expression and function in myositis biopsy sections.
  
  
  METHODS
  Production of IFNβ was assessed in cultured myoblasts after stimulation with the TLR-3 agonist poly(I-C) or with cytokines involved in Th1 and Th17 differentiation. Expression of HLA class I molecules by myoblasts was analyzed by fluorescence-activated cell sorting after activation of TLR-3 and IFNβ neutralization. In muscle biopsy samples from patients with polymyositis or dermatomyositis, expression of IFNβ, CD56 (a marker of immature muscle precursors), and HLA class I was analyzed using immunohistochemistry. Inflammatory infiltrates were characterized for the expression of myeloid dendritic cells (DCs), their associated CLRs, and the products of activated DCs, interleukin-12 (IL-12), and IL-23.
  
  
  RESULTS
  In cultured myoblasts, stimulation of TLR-3 induced the production of IFNβ when combined with IFNγ and up-regulated the expression of HLA class I molecules, which was decreased after IFNβ blockade. In myositis biopsy tissues, immature muscle precursors overexpressing HLA class I were identified as a source of IFNβ. CLRs associated with myeloid DCs were broadly expressed in inflammatory infiltrates, in association with IL-12 and IL-23, and with immature muscle precursors.
  
  
  CONCLUSIONS
  Immature muscle precursors may represent a local source of IFNβ and the target of an immune response involving activated DCs associated with the expression of CLRs and of IL-12 and IL-23, which are implicated in T cell polarization. In turn, such local production of IFNβ after TLR-3 activation in the presence of the Th1 cytokine IFNγ may explain HLA class I overexpression in myositis.
authors.affiliation: University of Lyon, Unit EA 4130 and Edouard Herriot Hospital, Lyon, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tournadre
authors.forename: Vanina
authors.initials: V
authors.lastname: Lenief
authors.forename: Assia
authors.initials: A
authors.lastname: Eljaafari
authors.forename: Pierre
authors.initials: P
authors.lastname: Miossec
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003882:Dermatomyositis / Q000378:metabolism*; D005260:Female; D005805:Genes, MHC Class I / Q000502:physiology*; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D032446:Myoblasts / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism; D017285:Polymyositis / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051196:Toll-Like Receptor 3; D016899:Interferon-beta