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

J Neuroimmunol. 2003 Aug;141(1-2):125-31. doi: 10.1016/s0165-5728(03)00218-2.


Because IFN-gamma-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-gamma 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-gamma 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-gamma 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.

MeSH terms

  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC / biosynthesis*
  • Chemokines, CXC / genetics
  • Culture Techniques
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / biosynthesis
  • Intercellular Signaling Peptides and Proteins / genetics
  • Interferon-gamma / pharmacology
  • Interferon-gamma / physiology*
  • Ligands
  • Muscle Fibers, Skeletal / immunology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / metabolism
  • Myositis, Inclusion Body / immunology*
  • RNA, Messenger / biosynthesis
  • Receptors, CXCR3
  • Receptors, Chemokine / biosynthesis
  • Receptors, Chemokine / genetics
  • Up-Regulation / immunology


  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL9
  • Chemokines, CXC
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • RNA, Messenger
  • Receptors, CXCR3
  • Receptors, Chemokine
  • Interferon-gamma