Expression of Toll-like receptor 3 and Toll-like receptor 7 in muscle is characteristic of inflammatory myopathy and is differentially regulated by Th1 and Th17 cytokines

Arthritis Rheum. 2010 Jul;62(7):2144-51. doi: 10.1002/art.27465.


Objective: To assess the expression of Toll-like receptor 3 (TLR-3) and TLR-7 in muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM) and to investigate the function and regulation of TLR-3 in cultured muscle cells.

Methods: The expression of TLR-3, TLR-7, HLA class I, and CD56, a marker of immature myoblast precursors, was analyzed using immunohistochemistry. TLR-3 regulation and signaling were assessed in myoblasts and in differentiated myotubes with the TLR-3 agonist poly(I-C), necrotic myoblasts, and Th1 and Th17 cytokines, in the presence or absence of neutralizing anti-TLR-3 antibody. Levels of TLR-3 messenger RNA (mRNA) were quantified by reverse transcription-polymerase chain reaction. Levels of interleukin-6 (IL-6), CCL20, and IL-8 were determined by enzyme-linked immunosorbent assay.

Results: TLR-3 and TLR-7 were expressed in PM/DM tissues, but not in noninflammatory muscle tissues, and were primarily detected in inflammatory infiltrates, although a few muscle cells were also positive. These TLR-3- and TLR-7-positive fibers expressed high levels of CD56 and HLA class I antigens. A synergy between poly(I-C) and IL-17 was observed for the production of IL-6 and CCL20. Similarly, stimulation with necrotic myoblasts increased IL-6 production, and stimulation with necrotic myoblasts in combination with IL-17 further increased the induction of IL-6. TLR-3 blockade decreased the inducing effect of necrotic myoblasts and IL-17 on IL-6 production. Stimulation with interferon-gamma (IFNgamma) increased TLR-3 mRNA levels, but IL-17 down-regulated the inducing effect of IFNgamma.

Conclusion: Our findings indicate that TLR-3 and TLR-7 are expressed in inflammatory myopathic tissues, particularly in immature myoblast precursors. Necrotic muscle cells activate cytokine production, in part, through the TLR-3 pathway, with a differential regulatory effect of Th1 and Th17 cytokines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / metabolism
  • Cytokines / pharmacology*
  • Dermatomyositis / immunology
  • Dermatomyositis / metabolism*
  • Dermatomyositis / pathology
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-17 / pharmacology
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Necrosis
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Helper-Inducer / pathology
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / metabolism*
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / metabolism*


  • Cytokines
  • IL17A protein, human
  • Interleukin-17
  • TLR3 protein, human
  • TLR7 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 7
  • Interferon-gamma