ArticlePharmaceuticals (Basel, Switzerland)2021
Valproic Acid Suppresses Autoimmune Recurrence and Allograft Rejection in Islet Transplantation through Induction of the Differentiation of Regulatory T Cells and Can Be Used in Cell Therapy for Type 1 Diabetes.
Article in Pharmaceuticals (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 10 citations in OpenAlex.
- Exploring the role of PD-1 as a marker in drug-refractory epilepsy and its potential indication for valproic acid treatment.Brain, behavior, & immunity - health · 2026Article
- Immune Infiltration-Related Genes as Potential Biomarkers and Predicted Targets for Renal Allograft Delayed Graft Function and Survival Outcome: An Integrated Machine Learning Approach and Drugs Analysis.Mediators of inflammation · 2026Article
- Microbial metabolic memory in inflammatory bowel disease: microbiota-derived metabolites, host-microbe reprogramming, and relapse susceptibility.Frontiers in microbiology · 2026Review
- Role of Treg cells in diabetes mellitus and association with traditional Chinese medicine: a literature review.Frontiers in immunology · 2026Review
- Pharmaco-Epigenetics and Epigenetic Drugs in Type 2 Diabetes: Can Epigenetics Predict Drug Efficiency?Biomedicines · 2025Review
- Neuro-immune-tumor axis in gliomas: a review of mechanisms, models, and translational opportunities.Frontiers in immunology · 2025Review
- Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study.Signal transduction and targeted therapy · 2023Review
- Islet allografts expressing a PD-L1 and IDO fusion protein evade immune rejection and reverse preexisting diabetes in immunocompetent mice without systemic immunosuppression.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Alpha-Lipoic Acid Inhibits Spontaneous Diabetes and Autoimmune Recurrence in Non-Obese Diabetic Mice by Enhancing Differentiation of Regulatory T Cells and Showed Potential for Use in Cell Therapies for the Treatment of Type 1 Diabetes.International journal of molecular sciences · 2022Article
- Mechanisms and therapeutic strategies of immune checkpoint molecules and regulators in type 1 diabetes.Frontiers in endocrinology · 2022Review
- Potential Therapeutic Application of Regulatory T Cells in Diabetes Mellitus Type 1.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Type 1 diabetes mellitus (T1D) results from the destruction of insulin-producing β cells in the islet of the pancreas by lymphocytes. Non-obese diabetic (NOD) mouse is an animal model frequently used for this disease. It has been considered that T1D is a T cell-mediated autoimmune disease. Both CD4+ and CD8+ T cells are highly responsible for the destruction of β cells within the pancreatic islets of Langerhans. Previous studies have revealed that regulatory T (Treg) cells play a critical role in the homeostasis of the immune system as well as immune tolerance to autoantigens, thereby preventing autoimmunity. Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Previous reports have demonstrated that VPA treatment decreases the incidence and severity of collagen-induced arthritis and experimental autoimmune neuritis by increasing the population of Treg cells in these mouse disease models. Given the effect of VPA in the induction of Treg cells' population, we evaluated the therapeutic potential and the protective mechanism of VPA treatment in the suppression of graft autoimmune rejection and immune recurrence in syngeneic or allogenic islet transplantation mouse models. In our study, we found that the treatment of VPA increased the expression of forkhead box P3 (FOXP3), which is a critical transcription factor that controls Treg cells' development and function. Our data revealed that 400 mg/kg VPA treatment in recipients effectively prolonged the survival of syngeneic and allogenic islet grafts. The percentage of Treg cells in splenocytes increased in VPA-treated recipients. We also proved that adoptive transfer of VPA-induced Tregs to the transplanted recipients effectively prolonged the survival of islet grafts. The results of this study provide evidence of the therapeutic potential and the underlying mechanism of VPA treatment in syngeneic islet transplantation for T1D. It also provides experimental evidence for cell therapy by adoptive transferring of in vitro VPA-induced Tregs for the suppression of autoimmune recurrence.
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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 OpenQuestion graph.