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.
Original language | English |
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Article number | 3317 |
Number of pages | 12 |
Journal | Nature Communications |
Volume | 9 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Dec 2018 |
Keywords
- 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
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