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The yin and yang of regulatory T cells and inflammation in RA

Nature Reviews Rheumatology volume 6, pages 572–577 (2010)Cite this article

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Abstract

Rheumatoid arthritis (RA) is characterized by chronic inflammation leading to joint destruction. Regulatory T (TREG) cells are potent suppressors of autoimmunity, but are not capable of controlling every aspect of the inflammatory reaction. We have found that TREG-cell function is abnormal in patients with RA, and that a distinct population of TREG cells with potent suppressive properties is induced after therapy with inhibitors of tumor necrosis factor. In this Review, we discuss the mutual interactions between the opposing forces of TREG cells and inflammation in the context of RA. Therapeutic approaches that enhance TREG-cell function whilst controlling inflammation are likely to be the most effective strategies for restoring immune tolerance in patients with this disease.

Key Points

  • The impaired function of naturally occurring regulatory T (TREG) cells in rheumatoid arthritis is linked to reduced expression of cytotoxic T-lymphocyte antigen 4

  • Therapy with inhibitors of tumor necrosis factor does not reverse this defect, but induces a novel TREG cell population with potent suppressive properties

  • Interleukin-17-producing helper T cells are resistant to suppression by TREG cells

  • Inflammation can subvert the function of TREG cells, resulting in the production of proinflammatory cytokines, which could have important implications for the development of cellular therapies

  • TREG cells can be therapeutically manipulated to enhance their function and stability

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Figure 1: TREG cells before and after anti-TNF therapy.
Figure 2: Epigenetic modification of FOXP3 expression influences TREG-cell stability.

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Acknowledgements

The authors are funded by grants from Arthritis Research UK.

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  1. Centre for Rheumatology Research, Windeyer Institute of Medical Science, University College London, 46 Cleveland Street, London, W1P 4JF, UK

    Clare A. Notley & Michael R. Ehrenstein

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Both authors contributed equally to researching data, discussing content and writing the article, and reviewing/editing the manuscript before submission.

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Correspondence to Michael R. Ehrenstein.

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Notley, C., Ehrenstein, M. The yin and yang of regulatory T cells and inflammation in RA. Nat Rev Rheumatol 6, 572–577 (2010). https://doi.org/10.1038/nrrheum.2010.143

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