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  • Review Article
  • Published:

The multifaceted biology of plasmacytoid dendritic cells

Key Points

  • This Review provides an introduction to human and mouse plasmacytoid dendritic cells (pDCs) and their importance in the immune system.

  • We discuss the phenotypes of human and mouse pDCs and the mechanisms that control their development.

  • We explain how pDCs sense nucleic acids and microbial products, as well as their potential role in viral infections and diseases characterized by a type I interferon (IFN) signature, such as systemic lupus erythematosus, psoriasis and type 1 diabetes.

  • We discuss the emerging field of microbiome research and how pDCs can shape mucosal immune responses.

  • We describe how pDCs can be tolerogenic or immunogenic in the context of cancer.

  • Finally, we end by raising several questions regarding the validity of targeting pDCs or their type I IFN production as a therapeutic strategy.

Abstract

Plasmacytoid dendritic cells (pDCs) are a unique DC subset that specializes in the production of type I interferons (IFNs). pDCs promote antiviral immune responses and have been implicated in the pathogenesis of autoimmune diseases that are characterized by a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. In this Review, we summarize recent progress in the field of pDC biology, focusing on the molecular mechanisms that regulate the development and functions of pDCs, the pathways involved in their sensing of pathogens and endogenous nucleic acids, their functions at mucosal sites, and their roles in infection, autoimmunity and cancer.

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Figure 1: Diverse functions of pDCs.
Figure 2: Regulation of pDC development and function.
Figure 3: Factors influencing pDC migration.
Figure 4: Toll-like receptor 9 signalling in pDCs.

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Acknowledgements

The authors greatly appreciate the feedback and helpful suggestions from M. Cella, S. Gilfillan, B. Reizis, M. Sanjuan and A. Krug. M.S. was supported by K01DK095972 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

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Correspondence to Marco Colonna.

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M.S. is currently a scientist at Janssen Research & Development, LLC. M.C. declares no competing interests.

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Star-form partner

The less abundant of the two strands of microRNA (miRNA) that are generated during miRNA biogenesis. Star-form miRNAs may have important functions in miRNA regulatory networks.

Non-canonical NF-κB pathway

Nuclear factor- κB (NF-κB) signalling that is induced by certain members of the tumour necrosis factor receptor superfamily and predominantly activates p52–RELB NF-κB complexes. By contrast, canonical (or classical) NF-κB signalling typically involves the activation of p50–RELA dimers and is induced by a wider range of pro-inflammatory stimuli.

B1a cells

A subset of innate-like B cells.

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Swiecki, M., Colonna, M. The multifaceted biology of plasmacytoid dendritic cells. Nat Rev Immunol 15, 471–485 (2015). https://doi.org/10.1038/nri3865

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