Abstract
Since the identification of interleukin (IL)-17 as a T-cell–derived cytokine 15 years ago, the contribution of the T-helper type 17 (Th17) pathway in inducing and maintaining chronic inflammation has been well-established, particularly in rheumatoid arthritis. In addition to the main Th1 profile first suggested to contribute to inflammatory myopathies, the presence in inflamed muscle tissue of myositis of IL-17–producing cells, in association with activated dendritic cells, suggests a local activation of the IL-23–Th17 pathway. IL-17 can act on muscle cells together with proinflammatory cytokines produced by monocytes and innate immunity to amplify the immune response that could lead to muscle destruction. Evidence for activation of the Th17 pathway in myositis lesions and in vitro effects of IL-17 on muscle cells suggest IL-17 as a therapeutic target. Inhibitors of IL-17 have been tested in other inflammatory conditions, but the position of IL-17 inhibition in the treatment of inflammatory myopathies remains to be defined.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
• Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med. 2009;361:888–98. This review describes the origin and functions of IL-17 and Th17 cells.
Zrioual S, Ecochard R, Tournadre A, Lenief V, Cazalis MA, Miossec P. Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. J Immunol. 2009;182:3112–20.
Zrioual S, Toh ML, Tournadre A, Zhou Y, Cazalis MA, Pachot A, Miossec V. Miossec P IL-17RA and IL-17RC receptors are essential for IL-17A-induced ELR + CXC chemokine expression in synoviocytes and are overexpressed in rheumatoid blood. J Immunol. 2008;180:655–63.
Tournadre A, Miossec P. Cytokine response in inflammatory myopathies. Curr Rheumatol Rep. 2007;9:286–90.
Chevrel G, Page G, Granet C, Streichenberger N, Varennes A, Miossec P. Interleukin-17 increases the effects of IL-1 beta on muscle cells: arguments for the role of T cells in the pathogenesis of myositis. J Neuroimmunol. 2003;137:125–33.
Chevrel G, Granet C, Miossec P. Contribution of tumour necrosis factor alpha and interleukin (IL) 1beta to IL6 production, NF-kappaB nuclear translocation, and class I MHC expression in muscle cells: in vitro regulation with specific cytokine inhibitors. Ann Rheum Dis. 2005;64:1257–62.
Nagaraju K, Casciola-Rosen L, Lundberg I, Rawat R, Cutting S, Thapliyal R, Chang J, Dwivedi S, Mitsak M, Chen YW, Plotz P, Rosen A, Hoffman E, Raben N. Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction. Arthritis Rheum. 2005;52:1824–35.
Li YP, Reid MB. Effect of tumor necrosis factor-alpha on skeletal muscle metabolism. Curr Opin Rheumatol. 2001;13:483–7.
Austin L, Bower J, Kurek J, Vakakis N. Effects of leukaemia inhibitory factor and other cytokines on murine and human myoblast proliferation. J Neurol Sci. 1992;112:185–91.
Eloranta ML, Barbasso Helmers S, Ulfgren AK, Rönnblom L, Alm GV, Lundberg IE. A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti-Jo-1 or anti-Ro 52/anti-Ro 60 autoantibodies. Arthritis Rheum. 2007;56:3112–24.
•• Tournadre A, Lenief V, Miossec P. Expression of TLR3 and TLR7 in muscle is characteristic of inflammatory myopathy and is differentially regulated by Th1 and Th17 cytokines. Arthritis Rheum. 2010;62:2144–51. This study reports the synergistic effect of IL-17 with TLR3 activation on the IL-6 and CCL20 production by muscle cells and the differential contribution of Th1 and Th17 cytokines in the regulation of TLR3 expression.
•• Tournadre A, Lenief V, Eljaafari-Dany A, Miossec P. Immature muscle precursors are a source of IFNβ in myositis: role of TLR3 activation and contribution to HLA class I up-regulation. Arthritis Rheum 2011; Sep 14. doi:10.1002/art.33350. [Epub ahead of print]. This study reports the role of TLR3 activation and immature muscle precursors in myositis pathogenesis. The detection of activated DCs expressing CLRs and associated with expression of IL-12 and IL-23 cytokines involved in Th1 and Th17 polarization is identified.
Toh ML, Kawashima M, Zrioual S, Hot A, Miossec P, Miossec P. IL17 inhibits human Th1 differentiation through IL12R beta 2 downregulation. Cytokine. 2009;48:226–30.
Page G, Chevrel G, Miossec P. Anatomic localization of immature and mature dendritic cell subsets in dermatomyositis and polymyositis: interaction with chemokines and Th1 cytokine-producing cells. Arthritis Rheum. 2004;50:199–208.
• Tournadre A, Porcherot M, Chérin P, Marie I, Hachulla E, Miossec P. Th1 and Th17 balance in inflammatory myopathies: interaction with dendritic cells and possible link with response to high-dose immunoglobulins. Cytokine. 2009;46:297–301. This study reports the presence of IL-17–producing cells in myositis muscle but a main Th1 profile. The detection of immature and mature DCs is identified in muscle biopsies from PM and DM patients.
Kondo M, Murakawa Y, Harashima N, Kobayashi S, Yamaguchi S, Harada M. Roles of proinflammatory cytokines and the Fas/Fas ligand interaction in the pathogenesis of inflammatory myopathies. Immunology. 2009;128:589–99.
Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH, Durez P, et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 2010;2:52ra72.
Chabaud M, Miossec P. The combination of tumor necrosis factor alpha blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflammation and bone resorption in an ex vivo model. Arthritis Rheum. 2001;44:1293–303.
Ohyanagi N, Ishido M, Suzuki F, Kaneko K, Kubota T, Miyasaka N, Nanki T. Retinoid ameliorates experimental autoimmune myositis, with modulation of Th cell differentiation and antibody production in vivo. Arthritis Rheum. 2009;60:3118–27.
Disclosure
No potential conflicts of interest relevant to this article were reported.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tournadre, A., Miossec, P. Interleukin-17 in Inflammatory Myopathies. Curr Rheumatol Rep 14, 252–256 (2012). https://doi.org/10.1007/s11926-012-0242-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11926-012-0242-x