ArticlePloS one2014
Dynamic cross talk model of the epithelial innate immune response to double-stranded RNA stimulation: coordinated dynamics emerging from cell-level noise.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Article
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- Cooperative interaction of interferon regulatory factor -1 and bromodomain-containing protein 4 on RNA polymerase activation for intrinsic innate immunity.Frontiers in immunology · 2024Article
- High-resolution kinetic characterization of the RIG-I-signaling pathway and the antiviral response.Life science alliance · 2023Article
- Innate Immunity, Epithelial Plasticity, and Remodeling in Asthma.Advances in experimental medicine and biology · 2023Article
- Article
- Early innate immune response triggered by the human respiratory syncytial virus and its regulation by ubiquitination/deubiquitination processes.Journal of biomedical science · 2022Review
- Innate Immune Responses to RSV Infection Facilitated by OGG1, an Enzyme Repairing Oxidatively Modified DNA Base Lesions.Journal of innate immunity · 2022Article
- Evolution of proteomics technologies for understanding respiratory syncytial virus pathogenesis.Expert review of proteomics · 2021Article
- The Hexosamine Biosynthetic Pathway Links Innate Inflammation With Epithelial-Mesenchymal Plasticity in Airway Remodeling.Frontiers in pharmacology · 2021Review
- RSV Reprograms the CDK9•BRD4 Chromatin Remodeling Complex to Couple Innate Inflammation to Airway Remodeling.Viruses · 2020Review
- More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis.Frontiers in immunology · 2020Review
- Pharmacoproteomics reveal novel protective activity of bromodomain containing 4 inhibitors on vascular homeostasis in TLR3-mediated airway remodeling.Journal of proteomics · 2019Article
- Efficacy of Novel Highly Specific Bromodomain-Containing Protein 4 Inhibitors in Innate Inflammation-Driven Airway Remodeling.American journal of respiratory cell and molecular biology · 2019Article
- Therapeutic targets for inflammation-mediated airway remodeling in chronic lung disease.Expert review of respiratory medicine · 2018Review
- Interferon-stimulated genes: new platforms and computational approaches.Mammalian genome : official journal of the International Mammalian Genome Society · 2018Review
- Central Role of the NF-κB Pathway in theJournal of virology · 2018Article
- Selective Antagonists of the Bronchiolar Epithelial NF-κB-Bromodomain-Containing Protein 4 Pathway in Viral-Induced Airway Inflammation.Cell reports · 2018Article
- Cell fate in antiviral response arises in the crosstalk of IRF, NF-κB and JAK/STAT pathways.Nature communications · 2018Article
- Systematic Analysis of Cell-Type Differences in the Epithelial Secretome Reveals Insights into the Pathogenesis of Respiratory Syncytial Virus-Induced Lower Respiratory Tract Infections.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
We present an integrated dynamical cross-talk model of the epithelial innate immune response (IIR) incorporating RIG-I and TLR3 as the two major pattern recognition receptors (PRR) converging on the RelA and IRF3 transcriptional effectors. bioPN simulations reproduce biologically relevant gene-and protein abundance measurements in response to time course, gene silencing and dose-response perturbations both at the population and single cell level. Our computational predictions suggest that RelA and IRF3 are under auto- and cross-regulation. We predict, and confirm experimentally, that RIG-I mRNA expression is controlled by IRF7. We also predict the existence of a TLR3-dependent, IRF3-independent transcription factor (or factors) that control(s) expression of MAVS, IRF3 and members of the IKK family. Our model confirms the observed dsRNA dose-dependence of oscillatory patterns in single cells, with periods of 1-3 hr. Model fitting to time series, matched by knockdown data suggests that the NF-κB module operates in a different regime (with different coefficient values) than in the TNFα-stimulation experiments. In future studies, this model will serve as a foundation for identification of virus-encoded IIR antagonists and examination of stochastic effects of viral replication. Our model generates simulated time series, which reproduce the noisy oscillatory patterns of activity (with 1-3 hour period) observed in individual cells. Our work supports the hypothesis that the IIR is a phenomenon that emerged by evolution despite highly variable responses at an individual cell level.
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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.