ArticleThe EMBO journal2013
Toll-like receptor-mediated IRE1α activation as a therapeutic target for inflammatory arthritis.
Article in The EMBO journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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The trial behind it
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Who cites it
138 citing papers in PubMed, 213 citations in OpenAlex.
- Overexpression of Synoviolin and miR-125a-5p, miR-19b-3p in peripheral blood of rheumatoid arthritis patients after treatment with conventional DMARDs and methylprednisolone.Clinical rheumatology · 2024Trial
- Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.The FEBS journal · 2026Review
- Spatial and functional characterization of ER stress proteins links fibroblast plasticity and proliferative processes in human osteoarthritic synovitis.Cell death and differentiation · 2026Article
- The IRE1-XBP1s Axis Drives Inflammatory Osteolysis by Regulating a 5-HT Dependent Endogenous Anti-Autophagy Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular Responses to Flavivirus Infections: Stress Signaling at the Crossroads of Host Defense and Virus Infection.Viruses · 2026Review
- Endoplasmic reticulum stress and the unfolded protein response in lung diseases: molecular pathways and therapeutic interventions.The Journal of pathology · 2026Review
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- IRE1/p‑JNK/NRF2 axis-mediated GPX4 upregulation underlies ferroptosis resistance in rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2026Article
- Endothelial IRE1 signaling maintains blood-brain barrier integrity and limits neuroinflammation after traumatic brain injury.Cell death & disease · 2026Article
- The IRE1α Pathway Links Endoplasmic Reticulum Stress to Atherosclerosis-Related Inflammation and Lipid Accumulation.Mediators of inflammation · 2026Article
- Dietary saturated fatty acids promote lung myeloid cell inflammasome activation and IL-1β-mediated inflammation in mice and humans.Science translational medicine · 2025Article
- Endoplasmic Reticulum Stress and Unfolded Protein Response Sensor ERN1 Regulates Organic Dust Induction of Lung Inflammation.FASEB bioAdvances · 2025Article
- IRE1α promotes phagosomal calcium flux to enhance macrophage fungicidal activity.Cell reports · 2025Article
- Microglial ER stress response via IRE1α regulates diet-induced metabolic imbalance and obesity in mice.Molecular metabolism · 2025Article
- Neutrophils: a Central Point of Interaction Between Immune Cells and Nonimmune Cells in Rheumatoid Arthritis.Clinical reviews in allergy & immunology · 2025Review
- Unfolded protein responses: Dynamic machinery in wound healing.Pharmacology & therapeutics · 2025Review
- Effects of Heparan Sulfate Trisaccharide Containing Oleanolic Acid in Attenuating Hyperphosphorylated Tau-Induced Cell Dysfunction Associated with Alzheimer's Disease.Journal of medicinal chemistry · 2025Article
- 4-Phenyl Butyric Acid (4-PBA) Suppresses Neutrophil Recruitment in a Murine Model of Acute Perinatal Inflammation.Journal of immunology research · 2025Article
- Inhalation exposure to airborne PMAmerican journal of physiology. Cell physiology · 2025Article
- Possible Involvement of X-Box Binding Protein-1 in the Onset of Pulpitis.European endodontic journal · 2024Article
78 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
23 authors at 9 institutions in 2 countries.
Funding
Abstract
In rheumatoid arthritis (RA), macrophage is one of the major sources of inflammatory mediators. Macrophages produce inflammatory cytokines through toll-like receptor (TLR)-mediated signalling during RA. Herein, we studied macrophages from the synovial fluid of RA patients and observed a significant increase in activation of inositol-requiring enzyme 1α (IRE1α), a primary unfolded protein response (UPR) transducer. Myeloid-specific deletion of the IRE1α gene protected mice from inflammatory arthritis, and treatment with the IRE1α-specific inhibitor 4U8C attenuated joint inflammation in mice. IRE1α was required for optimal production of pro-inflammatory cytokines as evidenced by impaired TLR-induced cytokine production in IRE1α-null macrophages and neutrophils. Further analyses demonstrated that tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6) plays a key role in TLR-mediated IRE1α activation by catalysing IRE1α ubiquitination and blocking the recruitment of protein phosphatase 2A (PP2A), a phosphatase that inhibits IRE1α phosphorylation. In summary, we discovered a novel regulatory axis through TRAF6-mediated IRE1α ubiquitination in regulating TLR-induced IRE1α activation in pro-inflammatory cytokine production, and demonstrated that IRE1α is a potential therapeutic target for inflammatory arthritis.
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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.