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

Nat Commun. 2018 Aug 20;9(1):3317. doi: 10.1038/s41467-018-05784-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cellular Microenvironment
  • Cross-Priming
  • Dendritic Cells / metabolism*
  • Gene Expression Regulation
  • Humans
  • Interferon Type I / biosynthesis*
  • Jurkat Cells
  • Paracrine Communication*
  • Sequence Analysis, RNA
  • Single-Cell Analysis / methods*
  • Stochastic Processes
  • Toll-Like Receptors / metabolism


  • Interferon Type I
  • Toll-Like Receptors