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Mechanisms of Disease: transcription factors in inflammatory arthritis

Nature Clinical Practice Rheumatology volume 2, pages 434–442 (2006)Cite this article

Abstract

Studies on the pathogenesis of inflammatory arthritides have begun to delve into the molecular and cellular mechanisms behind the development of these diseases, and transcription factors, as key regulators of immune-effector-cell development and function, have received growing attention. Their involvement in immune cells, such as T and B lymphocytes, macrophages and neutrophils, and cells from diseased tissues, such as synoviocytes, has been investigated, revealing dominant roles for members of the nuclear factor κB family, signal-transducer and activator of transcription family, and activator protein 1 family. This review summarizes recent findings and current knowledge regarding the roles of transcription factors in inflammatory arthritis, as evidenced by both biological and genetic studies, and discusses the relevance of these findings for anti-inflammatory therapies.

Key Points

  • Key roles have been identified in the pathogenesis of inflammatory arthritis for transcription factors, particularly members of the nuclear factor κB family, signal transducer and activator of transcription family, and activator protein 1 family

  • Additional transcription factors, such as interferon regulatory factor and nuclear factor of activated T cell family members, probably contribute to disease pathogenesis

  • Genetic studies have revealed associations between rheumatoid arthritis and polymorphisms in transcription factor binding sites and/or genes that regulate transcription factor activity

  • Effective therapies for inflammatory arthritis inhibit transcription factors known to have key roles in the pathogenesis of arthritis, including nuclear factor κB and activator protein 1

  • Novel therapies in arthritis are likely to continue to affect well-established transcription factors, but will probably target additional transcription factor pathways as well, such as signal-transducer and activator of transcription or Forkhead

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Figure 1: Transcription-factor pathways in inflammatory arthritis.

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Acknowledgements

We thank Christina Pioppi for assistance with literature review, as well as the authors of the many primary manuscripts which formed the basis of this review but were unable to be cited here for space considerations.

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Authors and Affiliations

  1. Research Scientist at Roche Palo Alto, Palo Alto, CA, USA

    Dee Aud & Stanford L Peng

  2. Director of Arthritis Research,

    Dee Aud & Stanford L Peng

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  1. Dee Aud
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Correspondence to Stanford L Peng.

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Aud, D., Peng, S. Mechanisms of Disease: transcription factors in inflammatory arthritis. Nat Rev Rheumatol 2, 434–442 (2006). https://doi.org/10.1038/ncprheum0222

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