Expression of IFN-γ-inducible chemokines in inclusion body myositis

Raghavanpillai Raju, Olavo Vasconcelos, Rebekah Granger, Marinos C. Dalakas

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Because IFN-γ-inducible chemokines, Mig (CXCL9), IP-10 (CXCL10), I-TAC (CXCL11) and their receptor, CXCR3, are critical molecules in T cell trafficking and generation of effector T cells, we examined their expression in the muscle biopsies of patients with sporadic inclusion body myositis (s-IBM) and disease controls. The functional role of these molecules was also studied by examining the effect and time kinetics of IFN-γ in inducing Mig and IP-10 expression in human myotubes in vitro. We found significantly high levels of Mig and IP-10 mRNA expression in s-IBM muscles compared to controls. IFN-γ upregulated the mRNA expression of Mig and IP-10 by human myotubes in a dose-dependent manner. By double-label immunohistochemistry, Mig was expressed on a subset of CD8+ cells and the areas of the muscle fiber in contact or contiguous to the T cells; CXCR3 was expressed only on a subset of the autoinvasive CD8+ T cells but not the myofibers. IP-10 and I-TAC were not detected by immunocytochemistry. The findings indicate that in s-IBM, IFN-γ is involved in the upregulation and in situ production of proinflammatory chemokines, which, in turn, participate in the recruitment of activated T cells and contribute to the self-sustaining nature of endomysial inflammation. Crown

Original languageEnglish (US)
Pages (from-to)125-131
Number of pages7
JournalJournal of Neuroimmunology
Volume141
Issue number1-2
DOIs
StatePublished - Aug 2003
Externally publishedYes

Keywords

  • CXCR3
  • Chemokines
  • IP-10
  • Inclusion body myositis
  • Mig
  • Myotube

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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