Spatiotemporal NF-kappa B dynamics encodes the position, amplitude, and duration of local immune inputs

Minjun Son, Tino Frank, Thomas Holst-Hansen, Andrew G. Wang, Michael Junkin, Sara S. Kashaf, Ala Trusina, Savas Tay*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

17 Citations (Scopus)
18 Downloads (Pure)

Abstract

Infected cells communicate through secreted signaling molecules like cytokines, which carry information about pathogens. How differences in cytokine secretion affect inflammatory signaling over space and how responding cells decode information from propagating cytokines are not understood. By computationally and experimentally studying NF-kappa B dynamics in cocultures of signal-sending cells (macrophages) and signal-receiving cells (fibroblasts), we find that cytokine signals are transmitted by wave-like propagation of NF-kappa B activity and create well-defined activation zones in responding cells. NF-kappa B dynamics in responding cells can simultaneously encode information about cytokine dose, duration, and distance to the cytokine source. Spatially resolved transcriptional analysis reveals that responding cells transmit local cytokine information to distance-specific proinflammatory gene expression patterns, creating "gene expression zones." Despite single-cell variability, the size and duration of the signaling zone are tightly controlled by the macrophage secretion profile. Our results highlight how macrophages tune cytokine secretion to control signal transmission distance and how inflammatory signaling interprets these signals in space and time.

Original languageEnglish
Article number6240
JournalScience Advances
Volume8
Issue number35
Number of pages14
ISSN2375-2548
DOIs
Publication statusPublished - 2 Sep 2022

Keywords

  • DIFFERENTIAL EXPRESSION ANALYSIS
  • TEMPORAL CONTROL
  • GENE-EXPRESSION
  • KINASE-ACTIVITY
  • INFORMATION
  • ALPHA
  • TNF
  • PROPAGATION
  • SPECIFICITY

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