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

Florian Wimmers, Nikita Subedi, Nicole van Buuringen, Daan Heister, Judith Vivié, Inge Beeren-Reinieren, Rob Woestenenk, Harry Dolstra, Aigars Piruska, Joannes F.M. Jacobs, Alexander van Oudenaarden, Carl G. Figdor, Wilhelm T.S. Huck, I. Jolanda M. de Vries, Jurjen Tel

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

41 Citaten (Scopus)
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Samenvatting

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.

Originele taal-2Engels
Artikelnummer3317
Aantal pagina's12
TijdschriftNature Communications
Volume9
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 1 dec 2018

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