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Dendritic cells as targets for therapy in rheumatoid arthritis

Nature Reviews Rheumatology volume 5, pages 566–571 (2009)Cite this article

Abstract

Dendritic cells (DCs) are central in inducing immunity and in mediating immune tolerance in their role as professional antigen-presenting cells. In the absence of DCs, a fatal autoimmunity develops in animal models. Although the role of DCs has been investigated extensively in the pathogenesis of rheumatoid arthritis (RA), it remains unclear whether DCs initiate autoimmunity in this disease. Nevertheless, evidence points towards a significant role for DCs in disease maintenance and progression. Current biologic therapies target cytokine products of antigen-presenting cells, such as tumor necrosis factor, interleukin-1 and interleukin-6. Emerging therapies for RA exploit the tolerogenic capacity of DCs. 'Tolerogenic' DCs can be generated from myeloid precursors ex vivo, loaded with antigen, and manipulated to suppress autoimmune responses in vivo, through the induction of activation-induced cell death, anergy, and/or regulatory T cells. Cells that are primed by DCs, such as B cells, type 1 and type 17 T helper cells, and that have been implicated in certain models of autoimmunity, are also being considered as additional targets for immune-based therapy. Studies to validate these approaches to ameliorate autoimmunity will be necessary before their application in the clinic.

Key Points

  • Dendritic cells (DCs) are implicated in the pathogenesis of rheumatoid arthritis (RA)

  • These cells and their products, such as tumor necrosis factor, interleukin-1 and interleukin-6, localize in rheumatoid synovium

  • The proinflammatory products of DCs can be targeted to ameliorate RA

  • DCs can also be manipulated to induce tolerance in animal models; studies are underway to test their tolerogenic activity in patients with RA

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Figure 1: DCs: mediators of immunity and tolerance.

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Acknowledgements

The author thanks Cynthia Magro, William St. Clair, Jonathan Poe, David Pisetsky, Karen Haas, Damian Maseda, and Takashi Matsushita for their assistance and suggestions. This work was supported by grants from the National Institutes of Health (AI56363, CA105001, CA96547, and AI057157).

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Authors and Affiliations

  1. Cancer Institute, New York University Langone Medical Center, New York, NY, USA

    Shaukat Khan & Nina Bhardwaj

  2. New York University Hospital for Joint Diseases, New York, NY, USA

    Jeffrey D. Greenberg

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Correspondence to Nina Bhardwaj.

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Khan, S., Greenberg, J. & Bhardwaj, N. Dendritic cells as targets for therapy in rheumatoid arthritis. Nat Rev Rheumatol 5, 566–571 (2009). https://doi.org/10.1038/nrrheum.2009.185

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