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
Article first published online: 22 MAR 2010
Copyright © 2010 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 62, Issue 7, pages 2144–2151, July 2010
How to Cite
Tournadre, A., Lenief, V. and Miossec, P. (2010), 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 & Rheumatism, 62: 2144–2151. doi: 10.1002/art.27465
- Issue published online: 29 JUN 2010
- Article first published online: 22 MAR 2010
- Manuscript Accepted: 12 MAR 2010
- Manuscript Received: 13 NOV 2009
- Interregional Programme Hospitalier de Recherche Clinique to the Centre Hospitalier Universitaire Clermont-Ferrand
- Region Rhône-Alpes
- Hospices Civils de Lyon
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.
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.
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-γ (IFNγ) increased TLR-3 mRNA levels, but IL-17 down-regulated the inducing effect of IFNγ.
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.