ArticleJCI insight2019
The E3 ligase Hrd1 stabilizes Tregs by antagonizing inflammatory cytokine-induced ER stress response.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 58 citations in OpenAlex.
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Unconventional role of hydroxymethylglutaryl-CoA synthase 1 in driving pathogenic TScience advances · 2026Article
- Review
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Endoplasmic reticulum stress as a mechanistic link between nutrition and inflammatory bowel disease.Frontiers in nutrition · 2026Review
- FOXP3 Stability-Adaptation Paradox: Reshaping Treg-Based Therapies for Intestinal Diseases.International journal of biological sciences · 2026Review
- Endoplasmic reticulum stress in Hashimoto's thyroiditis: a candidate amplification node linking thyroid-specific vulnerability and immune dysregulation.Frontiers in immunology · 2026Review
- 1-Nitropyrene induces acute lung injury via SYVN1/Caspase-11-mediated apoptosis and pyroptosis in pulmonary epithelial cells.Frontiers in pharmacology · 2026Article
- ER stress induced mitochondrial dysfunction drives Treg instability in coronary artery disease.EMBO molecular medicine · 2025Article
- Identification of immune signatures associated with both SARS-CoV-2 infection and lung transplantation.Cell reports. Medicine · 2025Article
- SEL1L-HRD1-mediated ERAD in mammals.Nature cell biology · 2025Review
- Succinate drives gut inflammation by promoting FOXP3 degradation through a molecular switch.Nature immunology · 2025Article
- TMED4 facilitates regulatory T cell suppressive function via ROS homeostasis in tumor and autoimmune mouse models.The Journal of clinical investigation · 2024Article
- IRE1α pathway: A potential bone metabolism mediator.Cell proliferation · 2024Review
- Regulatory T lymphocytes as a treatment method for rheumatoid arthritis - Superiority of allogeneic to autologous cells.Heliyon · 2024Review
- Endoplasmic Reticulum Stress in Hypertension and Salt Sensitivity of Blood Pressure.Current hypertension reports · 2024Review
- ER-associated degradation adapter Sel1L is required for CD8Cell reports · 2024Article
- HRD1-induced TMEM2 ubiquitination promotes ER stress-mediated apoptosis through a non-canonical pathway in intestinal ischemia/reperfusion.Cell death & disease · 2024Article
- Unfolded protein responses in T cell immunity.Frontiers in immunology · 2024Review
- Immunologic Crosstalk of Endoplasmic Reticulum Stress Signaling in Bladder Cancer.Current cancer drug targets · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Treg differentiation, maintenance, and function are controlled by the transcription factor FoxP3, which can be destabilized under inflammatory or other pathological conditions. Tregs can be destabilized under inflammatory or other pathological conditions, but the underlying mechanisms are not fully defined. Herein, we show that inflammatory cytokines induce ER stress response, which destabilizes Tregs by suppressing FoxP3 expression, suggesting a critical role of the ER stress response in maintaining Treg stability. Indeed, genetic deletion of Hrd1, an E3 ligase critical in suppressing the ER stress response, leads to elevated expression of ER stress-responsive genes in Treg and largely diminishes Treg suppressive functions under inflammatory condition. Mice with Treg-specific ablation of Hrd1 displayed massive multiorgan lymphocyte infiltration, body weight loss, and the development of severe small intestine inflammation with aging. At the molecular level, the deletion of Hrd1 led to the activation of both the ER stress sensor IRE1α and its downstream MAPK p38. Pharmacological suppression of IRE1α kinase, but not its endoribonuclease activity, diminished the elevated p38 activation and fully rescued the stability of Hrd1-null Tregs. Taken together, our studies reveal ER stress response as a previously unappreciated mechanism underlying Treg instability and that Hrd1 is crucial for maintaining Treg stability and functions through suppressing the IRE1α-mediated ER stress response.
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What Socratic 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 Socratic graph.