ArticleThe Journal of clinical investigation2021
Endoplasmic reticulum stress sensor IRE1α propels neutrophil hyperactivity in lupus.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 3 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Kidney involvement in VEXAS syndrome: insights from a rare case of secondary amyloidosis and systematic review of renal biopsy-confirmed reports.Clinical rheumatology · 2025Pooled it
- Diverse Roles of NETosis in the Pathogenesis of Lupus.Frontiers in immunology · 2022Pooled it
- Role of Neutrophils on the Ocular Surface.International journal of molecular sciences · 2021Pooled it
- TLR7/9 and type I interferon signaling reprogram neutrophil NET responses and impair antibacterial defense in systemic lupus erythematosus.Cell press blue · 2026Article
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Multifunctional nanotherapeutics for targeted modulation of endoplasmic reticulum stress to potentiate cancer therapy.Asian journal of pharmaceutical sciences · 2026Review
- Beyond bystanders: How β cell stress shapes the autoimmune response in T1D.Science translational medicine · 2026Review
- Prospective association between leukocyte telomere length and mortality: findings from the Black Women's Experiences Living with Lupus (BeWELL) Study.Clinical and experimental immunology · 2026Article
- Neutrophil extracellular traps in asthma and chronic obstructive pulmonary disease: pathogenic roles, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Mitochondrial reprogramming of neutrophil extracellular traps in chronic obstructive pulmonary disease and asthma: toward a phenotype-driven therapeutic framework.Frontiers in immunology · 2026Review
- A TLR7/9-IFNα-LDHB axis drives vital NET release and compromises antibacterial defense in lupus.bioRxiv : the preprint server for biology · 2025Article
- Article
- Live fast, die young: neutrophils streamline their metabolism to maximize inflammation.Infection and immunity · 2025Review
- Review
- Activation of the endoplasmic reticulum stress regulator IRE1α compromises pulmonary host defenses.Cell reports · 2025Article
- Accumulation of long-chain unsaturated fatty acids in the airway inflammatory microenvironment drives eosinophil etosis and corticosteroid resistance.Cell communication and signaling : CCS · 2025Article
- Mitochondria sense bacterial lactate and drive release of neutrophil extracellular traps.Cell host & microbe · 2025Article
- Gαq/11 aggravates acute lung injury in mice by promoting endoplasmic reticulum stress-mediated NETosis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Comprehensive Analysis of Ferroptosis Markers in Lupus Nephritis Based on Bioinformatics Analysis and Experimental Validation.Journal of inflammation research · 2025Article
- Endoplasmic reticulum stress and unfolded protein response in immune cell function.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Neutrophils amplify inflammation in lupus through the release of neutrophil extracellular traps (NETs). The endoplasmic reticulum stress sensor inositol-requiring enzyme 1 α (IRE1α) has been implicated as a perpetuator of inflammation in various chronic diseases; however, IRE1α has been little studied in relation to neutrophil function or lupus pathogenesis. Here, we found that neutrophils activated by lupus-derived immune complexes demonstrated markedly increased IRE1α ribonuclease activity. Importantly, in neutrophils isolated from patients with lupus, we also detected heightened IRE1α activity that was correlated with global disease activity. Immune complex-stimulated neutrophils produced both mitochondrial ROS (mitoROS) and the activated form of caspase-2 in an IRE1α-dependent fashion, whereas inhibition of IRE1α mitigated immune complex-mediated NETosis (in both human neutrophils and a mouse model of lupus). Administration of an IRE1α inhibitor to lupus-prone MRL/lpr mice over 8 weeks reduced mitoROS levels in peripheral blood neutrophils, while also restraining plasma cell expansion and autoantibody formation. In summary, these data identify a role for IRE1α in the hyperactivity of lupus neutrophils and show that this pathway is upstream of mitochondrial dysfunction, mitoROS formation, and NETosis. We believe that inhibition of the IRE1α pathway is a novel strategy for neutralizing NETosis in lupus, and potentially other inflammatory conditions.
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Registered trials
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