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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Wimmers F,Subedi N,van Buuringen N,Heister D,Vivié J,Beeren-Reinieren I,Woestenenk R,Dolstra H,Piruska A,Jacobs JFM,van Oudenaarden A,Figdor CG,Huck WTS,de Vries IJM,Tel Jdoi
10.1038/s41467-018-05784-3subject
Has Abstractpub_date
2018-08-20 00:00:00pages
3317issue
1issn
2041-1723pii
10.1038/s41467-018-05784-3journal_volume
9pub_type
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