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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

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

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.

OriginalsprogEngelsk
Artikelnummer6240
TidsskriftScience Advances
Vol/bind8
Udgave nummer35
Antal sider14
ISSN2375-2548
DOI
StatusUdgivet - 2 sep. 2022

ID: 325332475