ArticleThe Journal of clinical investigation2015
GP96 is a GARP chaperone and controls regulatory T cell functions.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 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.
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Who cites it
68 citing papers in PubMed, 97 citations in OpenAlex.
- Heat Shock Protein 90: From Molecular Chaperone Function to Therapeutic Targeting in Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Altered phenotype and gene expression of regulatory T cells (Tregs) in children with Autism, and the relationship with comorbid gastrointestinal symptoms.Journal of neuroinflammation · 2026Article
- The chaperone GRP94 interacts with the proprotein convertase furin and regulates TGF-beta maturation in human primary M2 macrophages.Cell death discovery · 2025Article
- Targeting TGFβ docking receptor glycoprotein A repetitions predominant (GARP) via novel chimeric antigen receptor (CAR)-T cell platform to treat glioblastoma.Neuro-oncology · 2025Article
- Altered Phenotype and Gene Expression of Regulatory T cells (Tregs) in Children with Autism, and the Relationship with Comorbid Gastrointestinal Symptoms.Research square · 2025Article
- Article
- Hsp90Pharmaceuticals (Basel, Switzerland) · 2025Review
- Selective Inhibition of hsp90 Paralogs: Uncovering the Role of Helix 1 in Grp94-Selective Ligand Binding.Proteins · 2025Article
- Extrinsic and Cell-Intrinsic Stress in the Immune Tumor Micro-Environment.International journal of molecular sciences · 2024Review
- TMED4 facilitates regulatory T cell suppressive function via ROS homeostasis in tumor and autoimmune mouse models.The Journal of clinical investigation · 2024Article
- GRP94 promotes anoikis resistance and peritoneal metastasis through YAP/TEAD1 pathway in gastric cancer.iScience · 2024Article
- GRP94 is an IGF-1R chaperone and regulates beta cell death in diabetes.Cell death & disease · 2024Article
- Regulatory role of PI16 in autoimmune arthritis and intestinal inflammation: implications for Treg cell differentiation and function.Journal of translational medicine · 2024Article
- Structural transitions modulate the chaperone activities of Grp94.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Heat shock protein gp96 drives natural killer cell maturation and anti-tumor immunity by counteracting Trim28 to stabilize Eomes.Nature communications · 2024Article
- Unfolded protein responses in T cell immunity.Frontiers in immunology · 2024Review
- Article
- The biology and inhibition of glucose-regulated protein 94/gp96.Medicinal research reviews · 2022Review
- Transforming growth factor-β1 in regulatory T cell biology.Science immunology · 2022Review
- GARP as a Therapeutic Target for the Modulation of Regulatory T Cells in Cancer and Autoimmunity.Frontiers in immunology · 2022Review
8 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
12 authors at 2 institutions in 1 country.
Funding
Abstract
Molecular chaperones control a multitude of cellular functions via folding chaperone-specific client proteins. CD4+FOXP3+ Tregs play key roles in maintaining peripheral tolerance, which is subject to regulation by multiple molecular switches, including mTOR and hypoxia-inducible factor. It is not clear whether GP96 (also known as GRP94), which is a master TLR and integrin chaperone, controls Treg function. Using murine genetic models, we demonstrated that GP96 is required for Treg maintenance and function, as loss of GP96 resulted in instability of the Treg lineage and impairment of suppressive functions in vivo. In the absence of GP96, Tregs were unable to maintain FOXP3 expression levels, resulting in systemic accumulation of pathogenic IFN-γ-producing and IL-17-producing T cells. We determined that GP96 serves as an essential chaperone for the cell-surface protein glycoprotein A repetitions predominant (GARP), which is a docking receptor for latent membrane-associated TGF-β (mLTGF-β). The loss of both GARP and integrins on GP96-deficient Tregs prevented expression of mLTGF-β and resulted in inefficient production of active TGF-β. Our work demonstrates that GP96 regulates multiple facets of Treg biology, thereby placing Treg stability and immunosuppressive functions strategically under the control of a major stress chaperone.
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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.