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  • Review Article
  • Published:

Altered dendritic cell functions in autoimmune diseases: distinct and overlapping profiles

Nature Reviews Rheumatology volume 12, pages 703–715 (2016)Cite this article

Subjects

Key Points

  • Dendritic cells (DCs) have critical roles in autoimmune disorders and functional heterogeneity exist within each DC subset

  • Autoimmune diseases are associated with changes in DC distribution and function

  • Some DC functions are similarly altered in different autoimmune diseases, whereas other changes are more disease-specific

  • DCs can be manipulated to restore T-cell tolerance and modulate autoantibody production

Abstract

Dendritic cells (DCs) are central regulators of the balance between immunity and tolerance, and alteration of the specialized DC system is a common feature of both systemic and tissue-specific autoimmune diseases. Increasing evidence indicates that the heterogeneity and the remarkable functional diversity of DC subsets might be differentially affected in autoimmune disorders, which accounts for different pathologies. This Review discusses recent findings that support this concept and provides a new conceptual overview of the altered function and distribution of DCs in autoimmune disorders. The discussion will focus on systemic lupus erythematosus — a prototype of a multi-organ disease — as well as rheumatoid arthritis and idiopathic inflammatory myopathies, pathologies characterized by tissue-specific lesions. Studies on these diseases have revealed common and disease-specific changes in DC distribution and in critical DC functions, such as phagocytosis, cytokine secretion and migration. An improved understanding of the roles of altered DC distribution and/or disturbed key functions in these autoimmune diseases will pave the way for the development of new therapies aiming at reducing immunogenicity and at enhancing the tolerogenic capacity of DCs. Although some tolerogenic DCs have already been introduced in the clinic, the successful translation of other DC-based therapies will require considerable research efforts.

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Figure 1: Origin, distribution and migration of human dendritic cell subsets.
Figure 2: Involvement of plasmacytoid dendritic cells in the induction and amplification of autoimmunity in systemic lupus erythematosus.
Figure 3: Dendritic cell subsets in the rheumatoid arthritis synovium and inflamed muscle.
Figure 4: Role of chemokines in dendritic cell migration.

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Authors and Affiliations

  1. Department of Immunobiology, University of Clermont Ferrand, Hôpital Gabriel Montpied, 58 rue de Montalembert, 630003, Clermont Ferrand, France

    Frédéric Coutant

  2. Department of Clinical Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon, Hôpital Edouard Herriot, 5 place d'Arsonval, Lyon, 69437, France

    Pierre Miossec

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All authors researched data for the article, made substantial contributions to discussions of content and wrote the manuscript. P.M. reviewed and edited the article before submission.

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Correspondence to Pierre Miossec.

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Coutant, F., Miossec, P. Altered dendritic cell functions in autoimmune diseases: distinct and overlapping profiles. Nat Rev Rheumatol 12, 703–715 (2016). https://doi.org/10.1038/nrrheum.2016.147

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