Key Points
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The IL-23–IL-17 axis is critically involved in the development of autoimmunity
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Tissue-specific IL-17A expression exacerbates tissue damage and disease chronicity
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The roles of IL-23 and IL-17 at different stages in the development and progression of rheumatoid arthrits (RA) and spondyloarthritis needs further investigation
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Greater understanding of the role of the IL-23–IL-17 axis in RA as opposed to psoriatic arthritis and psoriasis is needed
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Early combination therapy neutralizing both TNF activity and the IL-17/TH17 pathway might be a successful approach to achieving stable remission in patients with autoimmune disease and might even prevent disease development
Abstract
The discovery that the IL-23–IL-17 immune pathway is involved in many models of autoimmune disease has changed the concept of the role of T-helper cell subsets in the development of autoimmunity. In addition to TH17 cells, IL-17 is also produced by other T cell subsets and innate immune cells; which of these IL-17-producing cells have a role in tissue inflammation, and the timing, location and nature of their role(s), is incompletely understood. The current view is that innate and adaptive immune cells expressing the IL-23 receptor become pathogenic after exposure to IL-23, but further investigation into the role of IL-23 and IL-17 at different stages in the development and progression of chronic (destructive) inflammatory diseases is needed. Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are the two most common forms of chronic immune-mediated inflammatory arthritis, and the IL-23–IL-17 axis is thought to have a critical role in both. This Review discusses the basic mechanisms of these cytokines in RA and SpA on the basis of findings from disease-specific animal models as well as human ex vivo studies. Promising therapeutic applications to modulate this immune pathway are in development or have already been approved. Blockade of IL-17 and/or TH17-cell activity in combination with anti-TNF therapy might be a successful approach to achieving stable remission or even prevention of chronic immune-mediated inflammatory diseases.
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Change history
15 September 2015
In Figure 2a of this Review, full protection against CIA was incorrectly stated as an effect of IL-17 deficiency instead of IL-17RA deficiency.
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Acknowledgements
The author acknowledges team members (past and present) of the Lubberts Lab and the collaborating clinicians and researchers for scientific interactions and helpful discussions regarding this topic, as well as the Dutch Arthritis Association for financial grant support in different projects related to this topic in the past 10 years.
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Lubberts, E. The IL-23–IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol 11, 415–429 (2015). https://doi.org/10.1038/nrrheum.2015.53
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DOI: https://doi.org/10.1038/nrrheum.2015.53
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