ArticleThe Journal of clinical investigation2024
TMED4 facilitates regulatory T cell suppressive function via ROS homeostasis in tumor and autoimmune mouse models.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- 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
- Hypertensive mt. tRNARedox biology · 2026Article
- Targeting TMED4 enhances CD8Science advances · 2026Article
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- The role of tumor metabolic reprogramming in acquired anti-PD-1/PD-L1 resistance.Translational lung cancer research · 2026Review
- IRE1-XBP1driven induction of TMED9 stabilizes ATF6 during ER stress to promote cell survival.Cellular & molecular biology letters · 2026Article
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- PET-microplastics trigger endothelial glycocalyx loss via ER stress and ROS unleashing IL-1β-driven SMC switching and early aortic structural impairment.Journal of nanobiotechnology · 2026Article
- Integrated single-cell multi-omics analysis unveils heterogeneity in the prostate cancer tumor microenvironment.Discover oncology · 2026Article
- Lipid Metabolism in Regulatory T Cells in Health and Disease.Journal of inflammation research · 2026Review
- Linoleic acid metabolic reprogramming is linked to immunometabolic remodeling and post-transplant recurrence risk in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- Redox-metabolic circuits as a central regulator of T cell-based immunotherapy.Frontiers in immunology · 2026Review
- FOXP3 Stability-Adaptation Paradox: Reshaping Treg-Based Therapies for Intestinal Diseases.International journal of biological sciences · 2026Review
- Associations between systemic immune-inflammation index and immune-related hypothyroidism in non-small cell lung cancer patients receiving immune checkpoint inhibitors: a retrospective study.Frontiers in oncology · 2026Article
- CD4Frontiers in psychiatry · 2026Article
- Endoplasmic reticulum stress in skeletal muscle dysfunction of type 2 diabetes: mechanisms and therapeutic implications.Frontiers in endocrinology · 2026Review
- Overcoming immunotherapy resistance in breast cancer: a novel strategy by targeting the integrated stress response.Frontiers in cell and developmental biology · 2026Review
- Fructose intake driven glycolysis-ROS-EGFR axis specifically promotes the generation and pathogenicity of Th17 cells.Nature communications · 2025Article
- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
Corrections and comments
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum stress (ERS) plays crucial roles in maintaining Treg stability and function, yet the underlying mechanism remains largely unexplored. Here, we demonstrate that (Tmed4ΔTreg) mice with Treg-specific KO of ERS-related protein transmembrane p24 trafficking protein 4 (TMED4) had more Tregs with impaired Foxp3 stability, Treg signatures, and suppressive activity, which led to T cell hyperactivation and an exacerbated inflammatory phenotype and boosted antitumor immunity in mice. Mechanistically, loss of Tmed4 caused defects in ERS and a nuclear factor erythroid 2-related factor 2-related (NRF2-related) antioxidant response, which resulted in excessive ROS that reduced the Foxp3 stability and suppressive function of Tregs in an IRE1α/XBP1 axis-dependent manner. The abnormalities could be effectively rescued by the ROS scavenger, NRF2 inducer, or by forcible expression of IRE1α. Moreover, TMED4 suppressed IRE1α proteosome degradation via the ER-associated degradation (ERAD) system including the ER chaperone binding immunoglobulin protein (BIP). Our study reveals that TMED4 maintained the stability of Tregs and their suppressive function through IRE1α-dependent ROS and the NRF2-related antioxidant response.
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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 Socratic graph.