ArticleScience signaling2014
Switching of the relative dominance between feedback mechanisms in lipopolysaccharide-induced NF-κB signaling.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
76 citing papers in PubMed, 120 citations in OpenAlex.
- Macrophage-Specific NF-κB Activation Dynamics Can Segregate Inflammatory Bowel Disease Patients.Frontiers in immunology · 2019Trial
- Dissection of MAPK and NF-κB p65 signaling dynamics underlying LPS tolerance in macrophages at the single-cell level.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Dysregulated NF-κB dynamics impair proteostasis and drive premature differentiation in aging B cell development.Cell press blue · 2026Article
- Autonomous Oscillations of NF-κB.Advances in experimental medicine and biology · 2026Review
- NF-κB epigenetic attractor landscape drives breast cancer heterogeneity.NPJ systems biology and applications · 2025Article
- Downregulated RSAD2 Attenuates the Apoptosis of LPS-Stimulated RAW264.7 via NF-κB Signaling Pathway.Journal of inflammation research · 2025Article
- Innate immune memory in chronic HIV and HIV-associated neurocognitive disorders (HAND): potential mechanisms and clinical implications.Journal of neurovirology · 2024Review
- Evidence of collective influence in innate sensing using fluidic force microscopy.Frontiers in immunology · 2024Article
- Reframing macrophage diversity with network motifs.Trends in immunology · 2023Review
- Article
- NF-κB dynamics in the language of immune cells.Trends in immunology · 2023Review
- Double knockin mice show NF-κB trajectories in immune signaling and aging.Cell reports · 2022Article
- Article
- Myeloid cell-specific topoisomerase 1 inhibition using DNA origami mitigates neuroinflammation.EMBO reports · 2022Article
- Functional Hallmarks of Healthy Macrophage Responses: Their Regulatory Basis and Disease Relevance.Annual review of immunology · 2022Review
- Post-transcriptional regulatory feedback encodes JAK-STAT signal memory of interferon stimulation.Frontiers in immunology · 2022Article
- Insights on the NF-κB System Using Live Cell Imaging: Recent Developments and Future Perspectives.Frontiers in immunology · 2022Review
- Progress and challenges in understanding the regulation and function of p53 dynamics.Biochemical Society transactions · 2021Review
- Review
- Inhibitory feedback control of NF-κB signalling in health and disease.The Biochemical journal · 2021Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
A fundamental goal in biology is to gain a quantitative understanding of how appropriate cell responses are achieved amid conflicting signals that work in parallel. Through live, single-cell imaging, we monitored both the dynamics of nuclear factor κB (NF-κB) signaling and inflammatory cytokine transcription in macrophages exposed to the bacterial product lipopolysaccharide (LPS). Our analysis revealed a previously uncharacterized positive feedback loop involving induction of the expression of Rela, which encodes the RelA (p65) NF-κB subunit. This positive feedback loop rewired the regulatory network when cells were exposed to LPS above a distinct concentration. Paradoxically, this rewiring of NF-κB signaling in macrophages (a myeloid cell type) required the transcription factor Ikaros, which promotes the development of lymphoid cells. Mathematical modeling and experimental validation showed that the RelA positive feedback overcame existing negative feedback loops and enabled cells to discriminate between different concentrations of LPS to mount an effective innate immune response only at higher concentrations. We suggest that this switching in the relative dominance of feedback loops ("feedback dominance switching") may be a general mechanism in immune cells to integrate opposing feedback on a key transcriptional regulator and to set a response threshold for the host.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.