ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Endoplasmic reticulum stress regulates the innate immunity critical transcription factor IRF3.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 149 citations in OpenAlex.
- Beyond the barrier: Engineering the tumor-immune-soil nexus-a mechanistic blueprint for integrating Traditional Chinese Medicine with immunotherapy in metastatic colorectal cancer.Medical oncology (Northwood, London, England) · 2026Review
- Non-canonical STING activation by calcium influx paired to endoplasmic reticulum stress.Cell communication and signaling : CCS · 2026Article
- The Role and Therapeutic Potential of the cGAS-STING Signaling Pathway in Alzheimer's Disease.Brain and behavior · 2025Review
- Article
- IRF3 in viral infections: more than just triggering the interferon response.Genes and immunity · 2025Review
- Antimicrobial peptide LL-37 increases rhinovirus-induced interferon β expression in human airway epithelial cells through a CaBiochemistry and biophysics reports · 2025Article
- Vamp3/syntaxin 4 mediates the basolateral membrane fusion of TfR transcytosis across the BBB and is exploited by pathogenicProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Palbociclib and dsRNA sensor co-operate to enhance anti-cancer effects through ER stress and modulation of immune evasion.Nature communications · 2025Article
- Bioactive metallic nanoparticles for synergistic cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Renal Ischemia Induces Endoplasmic Reticulum Stress and Impairs the Reparative Potency of Scattered Tubular-Like Cells.American journal of nephrology · 2025Article
- Crosstalk Between Cell Death and the cGAS-STING Pathway in Sepsis-Associated Acute Lung Injury.Journal of inflammation research · 2025Review
- H-151 attenuates lipopolysaccharide-induced acute kidney injury by inhibiting the STING-TBK1 pathway.Renal failure · 2024Article
- Tauroursodeoxycholic acid ameliorates renal injury induced by COL4A3 mutation.Kidney international · 2024Article
- Strategies for the development of metalloimmunotherapies.Nature biomedical engineering · 2024Review
- ER-transiting bacterial toxins amplify STING innate immune responses and elicit ER stress.Infection and immunity · 2024Article
- Gasdermin B, an asthma-susceptibility gene, promotes MAVS-TBK1 signalling and airway inflammation.The European respiratory journal · 2024Article
- Molecular mechanisms involved in alcohol craving, IRF3, and endoplasmic reticulum stress: a multi-omics study.Translational psychiatry · 2024Article
- Multiple unfolded protein response pathways cooperate to link cytosolic dsDNA release to stimulator of interferon gene activation.Frontiers in immunology · 2024Article
- The cGAS-STING pathway in viral infections: a promising link between inflammation, oxidative stress and autophagy.Frontiers in immunology · 2024Review
- Type I IFN signaling in the absence of IRGM1 promotesbioRxiv : the preprint server for biology · 2023Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
IFN regulatory factor 3 (IRF3) regulates early type I IFNs and other genes involved in innate immunity. We have previously shown that cells undergoing an endoplasmic reticulum (ER) stress response called the unfolded protein response produce synergistically augmented IFN-β when stimulated with pattern recognition receptor agonists such as LPS. Concomitant ER stress and LPS stimulation resulted in greater recruitment of the IRF3 transcription factor to ifnb1 gene regulatory elements. In this study, we used murine cells to demonstrate that both oxygen-glucose deprivation and pharmacologic unfolded protein response inducers trigger phosphorylation and nuclear translocation of IRF3, even in the absence of exogenous LPS. Different ER stressors used distinct mechanisms to activate IRF3: IRF3 phosphorylation due to calcium-mobilizing ER stress (thapsigargin treatment, oxygen-glucose deprivation) critically depended upon stimulator of IFN gene, an ER-resident nucleic acid-responsive molecule. However, calcium mobilization alone by ionomycin was insufficient for IRF3 phosphorylation. In contrast, other forms of ER stress (e.g., tunicamycin treatment) promote IRF3 phosphorylation independently of stimulator of IFN gene and TANK-binding kinase 1. Rather, IRF3 activation by tunicamycin and 2-deoxyglucose was inhibited by 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride, a serine protease inhibitor that blocks activating transcription factor 6 processing. Interfering with ER stress-induced IRF3 activation abrogated IFN-β synergy. Together, these data suggest ER stress primes cells to respond to innate immune stimuli by activating the IRF3 transcription factor. Our results also suggest certain types of ER stress accomplish IRF3 phosphorylation by co-opting existing innate immune pathogen response pathways. These data have implications for diseases involving ER stress and type I IFN.
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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.