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


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 TNF? 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.

SUBMITTER: Wimmers F 

PROVIDER: S-EPMC6102223 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Wimmers Florian F   Subedi Nikita N   van Buuringen Nicole N   Heister Daan D   Vivié Judith J   Beeren-Reinieren Inge I   Woestenenk Rob R   Dolstra Harry H   Piruska Aigars A   Jacobs Joannes F M JFM   van Oudenaarden Alexander A   Figdor Carl G CG   Huck Wilhelm T S WTS   de Vries I Jolanda M IJM   Tel Jurjen J  

Nature communications 20180820 1


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 c  ...[more]

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