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 wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

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
Pagina's (van-tot)3317
TijdschriftNature Communications
Volume9
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 20 aug 2018

Vingerafdruk

Duik in de onderzoeksthema's van 'Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells'. Samen vormen ze een unieke vingerafdruk.

Citeer dit