Spatiotemporal NF-kappa B dynamics encodes the position, amplitude, and duration of local immune inputs
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Spatiotemporal NF-kappa B dynamics encodes the position, amplitude, and duration of local immune inputs. / Son, Minjun; Frank, Tino; Holst-Hansen, Thomas; Wang, Andrew G.; Junkin, Michael; Kashaf, Sara S.; Trusina, Ala; Tay, Savas.
I: Science Advances, Bind 8, Nr. 35, 6240, 02.09.2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Spatiotemporal NF-kappa B dynamics encodes the position, amplitude, and duration of local immune inputs
AU - Son, Minjun
AU - Frank, Tino
AU - Holst-Hansen, Thomas
AU - Wang, Andrew G.
AU - Junkin, Michael
AU - Kashaf, Sara S.
AU - Trusina, Ala
AU - Tay, Savas
PY - 2022/9/2
Y1 - 2022/9/2
N2 - 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.
AB - 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.
KW - DIFFERENTIAL EXPRESSION ANALYSIS
KW - TEMPORAL CONTROL
KW - GENE-EXPRESSION
KW - KINASE-ACTIVITY
KW - INFORMATION
KW - ALPHA
KW - TNF
KW - PROPAGATION
KW - SPECIFICITY
U2 - 10.1126/sciadv.abn6240
DO - 10.1126/sciadv.abn6240
M3 - Journal article
C2 - 36044569
VL - 8
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 35
M1 - 6240
ER -
ID: 325332475