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Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells

Author

Listed:
  • Florian Wimmers

    (Radboud University Medical Center
    Stanford University)

  • Nikita Subedi

    (Eindhoven University of Technology
    Eindhoven University of Technology)

  • Nicole Buuringen

    (Radboud University Medical Center)

  • Daan Heister

    (Radboud University Medical Center)

  • Judith Vivié

    (Hubrecht Institute - KNAW and University Medical Center Utrecht)

  • Inge Beeren-Reinieren

    (Radboud University Medical Center)

  • Rob Woestenenk

    (Radboud University Medical Center)

  • Harry Dolstra

    (Radboud University Medical Center)

  • Aigars Piruska

    (Radboud University)

  • Joannes F. M. Jacobs

    (Radboud University Medical Center)

  • Alexander Oudenaarden

    (Hubrecht Institute - KNAW and University Medical Center Utrecht)

  • Carl G. Figdor

    (Radboud University Medical Center)

  • Wilhelm T. S. Huck

    (Radboud University)

  • I. Jolanda M. Vries

    (Radboud University Medical Center)

  • Jurjen Tel

    (Radboud University Medical Center
    Eindhoven University of Technology
    Eindhoven University of Technology)

Abstract

Type I interferon (IFN) is a key driver of immunity to infections and cancer. Plasmacytoid dendritic cells (pDCs) are uniquely equipped to produce large quantities of type I IFN but the mechanisms that control this process are poorly understood. Here we report on a droplet-based microfluidic platform to investigate type I IFN production in human pDCs at the single-cell level. We show that type I IFN but not TNFα production is limited to a small subpopulation of individually stimulated pDCs and controlled by stochastic gene regulation. Combining single-cell cytokine analysis with single-cell RNA-seq profiling reveals no evidence for a pre-existing subset of type I IFN-producing pDCs. By modulating the droplet microenvironment, we demonstrate that vigorous pDC population responses are driven by a type I IFN amplification loop. Our study highlights the significance of stochastic gene regulation and suggests strategies to dissect the characteristics of immune responses at the single-cell level.

Suggested Citation

  • Florian Wimmers & Nikita Subedi & Nicole Buuringen & Daan Heister & Judith Vivié & Inge Beeren-Reinieren & Rob Woestenenk & Harry Dolstra & Aigars Piruska & Joannes F. M. Jacobs & Alexander Oudenaarde, 2018. "Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05784-3
    DOI: 10.1038/s41467-018-05784-3
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    Cited by:

    1. Masayuki Nishide & Kei Nishimura & Hiroaki Matsushita & Ryuya Edahiro & Sachi Inukai & Hiroshi Shimagami & Shoji Kawada & Yasuhiro Kato & Takahiro Kawasaki & Kohei Tsujimoto & Hokuto Kamon & Ryusuke O, 2023. "Single-cell multi-omics analysis identifies two distinct phenotypes of newly-onset microscopic polyangiitis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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