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Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis

Nature Reviews Rheumatology volume 15, pages 9–17 (2019)Cite this article

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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a failure of spontaneous resolution of inflammation. Although the pro-inflammatory cytokines and mediators that trigger RA have been the focus of intense investigations, the regulatory and anti-inflammatory cytokines responsible for the suppression and resolution of disease in a context-dependent manner have been less well characterized. However, knowledge of the pathways that control the suppression and resolution of inflammation in RA is clinically relevant and conceptually important for understanding the pathophysiology of the disease and for the development of treatments that enable long-term remission. Cytokine-mediated processes such as the activation of T helper 2 cells by IL-4 and IL-13, the resolution of inflammation by IL-9, IL-5-induced eosinophil expansion, IL-33-mediated macrophage polarization, the production of IL-10 by regulatory B cells and IL-27-mediated suppression of lymphoid follicle formation are all involved in governing the regulation and resolution of inflammation in RA. By better understanding these immune-regulatory signalling pathways, new therapeutic strategies for RA can be envisioned that aim to balance and resolve, rather than suppress, inflammation.

Key points

  • Anti-inflammatory cytokines counterbalance the chronic activation of innate and adaptive immune cells in rheumatoid arthritis (RA).

  • Macrophage polarization towards an immune-regulatory phenotype is mediated by cytokines involved in type 2 immune responses and in eosinophil activation, such as IL-4, IL-5, IL-13 and IL-33.

  • Regulatory T cell activation in RA depends on the release of IL-9 from group 2 innate lymphoid cells.

  • Regulatory B cells are activated during inflammation and mitigate adaptive immune responses in experimental arthritis via the release of IL-10.

  • Inducing anti-inflammatory pathways and the resolution of inflammation is an attractive therapeutic option for patients with RA to achieve long-term disease control.

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Fig. 1: Involvement of IL-4, IL-13 and IL-5 in the inhibition of rheumatoid arthritis.
Fig. 2: Involvement of IL-33 and IL-9 in the resolution of rheumatoid arthritis.
Fig. 3: Immune regulation by IL-27 and IL-10 in rheumatoid arthritis.

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Acknowledgements

The work of the authors is supported by the National Natural Science Foundation of China (81501344 to Z.C.), the Natural Science Foundation of Anhui Province (1608085MH172 to Z.C.) and by the German Research Council (CRC1181 to A.B. and G.S. and SPP1937 to A.R.).

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, The First Affiliated Hospital of the University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

    Zhu Chen

  2. Department of Internal Medicine 3, Friedrich Alexander University Erlangen-Nuremberg and Universitatsklinikum Erlangen, Erlangen, Germany

    Aline Bozec, Andreas Ramming & Georg Schett

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  1. Zhu Chen
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  2. Aline Bozec
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Z.C. and G.S. wrote the article. All authors researched data for the article, made substantial contributions to discussions of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Georg Schett.

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Chen, Z., Bozec, A., Ramming, A. et al. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nat Rev Rheumatol 15, 9–17 (2019). https://doi.org/10.1038/s41584-018-0109-2

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