ArticleJCI insight2023
Rapamycin improves Graves' orbitopathy by suppressing CD4+ cytotoxic T lymphocytes.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Identification and Validation of Biomarkers in the Development and Progression of Graves' Ophthalmopathy.Investigative ophthalmology & visual science · 2026Article
- Serum mTOR: an associative marker of Graves' orbitopathy.Journal of endocrinological investigation · 2026Article
- Metabolic reprogramming of Th17/Treg imbalance in autoimmune thyroid diseases.Cell communication and signaling : CCS · 2026Review
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Beyond the Th2 paradigm: CD4+ cytotoxic T lymphocytes as key drivers of tissue damage and fibrosis in IgG4-related disease.Frontiers in immunology · 2026Review
- Vitamin D dynamics predict treatment response to intravenous glucocorticoids in thyroid-associated ophthalmopathy: a retrospective cohort study.Frontiers in immunology · 2026Article
- The therapeutic revolution in thyroid eye disease: from orbital radiotherapy to teprotumumab and AI.Frontiers in medicine · 2026Review
- Sirolimus for the treatment of Graves' orbitopathy.Thyroid research · 2025Review
- A Preclinical State of Graves' Ophthalmopathy Characterized by Hypoxia of T-cells Identified via Multiomics Analysis.The Journal of clinical endocrinology and metabolism · 2025Article
- Unravelling the pathogenic mechanisms in Graves' orbitopathy.European thyroid journal · 2025Review
- Rapamycin nanoparticles suppress autoreactive lymphocytes and reduce anti-mitochondrial antibodies in primary biliary cholangitis: Mechanisms and implications.World journal of hepatology · 2025Article
- Rapamycin reveals neuropeptide Y as a regulator of senescence and inflammatory pathways in arthritis.Neuropeptides · 2025Article
- Targeted immunotherapies for Graves' thyroidal & orbital diseases.Frontiers in immunology · 2025Review
- Negative association between serum calcium and glucocorticoid-induced hypertension in thyroid-associated ophthalmopathy patients treated with methylprednisolone.Frontiers in endocrinology · 2025Article
- Dynamic transition of Tregs to cytotoxic phenotype amid systemic inflammation in Graves' ophthalmopathy.JCI insight · 2024Article
- Evaluation of 99Tcm-DTPA orbit SPECT/CT combined with thyroid function test in the treatment of radioactive iodine I-131 in patients with thyroid-associated ophthalmopathy-hyperthyroidism.Journal of medical biochemistry · 2024Article
- Ocular surface and meibomian gland evaluation in euthyroid Graves' ophthalmopathy.International ophthalmology · 2024Article
- The role of autophagy in Graves disease: knowns and unknowns.Frontiers in cell and developmental biology · 2024Review
- Chimeric antigen receptor T-cell therapy in autoimmune diseases.Frontiers in immunology · 2024Review
- Defective LAT signalosome pathology in mice mimics human IgG4-related disease at single-cell level.The Journal of experimental medicine · 2023Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4+ cytotoxic T lymphocytes (CTLs) were recently implicated in immune-mediated inflammation and fibrosis progression of Graves' orbitopathy (GO). However, little is known about therapeutic targeting of CD4+ CTLs. Herein, we studied the effect of rapamycin, an approved mTOR complex 1 (mTORC1) inhibitor, in a GO mouse model, in vitro, and in patients with refractory GO. In the adenovirus-induced model, rapamycin significantly decreased the incidence of GO. This was accompanied by the reduction of both CD4+ CTLs and the reduction of orbital inflammation, adipogenesis, and fibrosis. CD4+ CTLs from patients with active GO showed upregulation of the mTOR pathway, while rapamycin decreased their proportions and cytotoxic function. Low-dose rapamycin treatment substantially improved diplopia and the clinical activity score in steroid-refractory patients with GO. Single-cell RNA-Seq revealed that eye motility improvement was closely related to suppression of inflammation and chemotaxis in CD4+ CTLs. In conclusion, rapamycin is a promising treatment for CD4+ CTL-mediated inflammation and fibrosis in GO.
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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.