ArticleCellular & molecular immunology2012
SAHA, an HDAC inhibitor, synergizes with tacrolimus to prevent murine cardiac allograft rejection.
Article in Cellular & molecular immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Porcine kidney xenotransplantation: From primate models to clinical reality.Animal models and experimental medicine · 2026Review
- Immunometabolism of Liver Xenotransplantation and Prospective Solutions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Repurposing Histone Deacetylase Inhibitors for Management of Solid Organ Transplant Rejection.Results and problems in cell differentiation · 2025Review
- Epigenetic regulation of tumor immunity.The Journal of clinical investigation · 2024Review
- Modulating Treg stability to improve cancer immunotherapy.Trends in cancer · 2023Review
- STXBP3 and GOT2 predict immunological activity in acute allograft rejection.Frontiers in immunology · 2022Article
- Single-cell transcriptomic identified HIF1A as a target for attenuating acute rejection after heart transplantation.Basic research in cardiology · 2021Article
- Review
- Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone.EMBO reports · 2020Article
- Histone Deacetylation Inhibitors as Modulators of Regulatory T Cells.International journal of molecular sciences · 2020Review
- The Fate of Th17 Cells is Shaped by Epigenetic Modifications and Remodeled by the Tumor Microenvironment.International journal of molecular sciences · 2020Review
- Restoring T Cell Tolerance, Exploring the Potential of Histone Deacetylase Inhibitors for the Treatment of Juvenile Idiopathic Arthritis.Frontiers in immunology · 2019Review
- Epigenetics in Cardiac Fibrosis: Emphasis on Inflammation and Fibroblast Activation.JACC. Basic to translational science · 2018Review
- Epigenetic alterations are associated with monocyte immune dysfunctions in HIV-1 infection.Scientific reports · 2018Article
- Sirtinol regulates the balance of Th17/Treg to prevent allograft rejection.Cell & bioscience · 2017Article
- Advances on Non-CD4 + Foxp3+ T Regulatory Cells: CD8+, Type 1, and Double Negative T Regulatory Cells in Organ Transplantation.Transplantation · 2015Review
- Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Suberoylanilide hydroxamic acid (SAHA), as a histone deacetylase (HDAC) inhibitor (HDACi), was recently found to exhibit an immunosuppressive effect. However, whether SAHA can synergize with calcineurin inhibitors (CNIs) to inhibit allograft rejection and its underlying mechanism remain elusive. In this study, we demonstrated the synergistic effects of SAHA and non-therapeutic dose of tacrolimus (FK506) in prolonging the allograft survival in a murine cardiac transplant model. Concomitant intragraft examination revealed that allografts from SAHA-treated recipients showed significantly lower levels of IL-17 expression, and no discernable difference for IL-17 expressions was detected between SAHA- and SAHA/FK506-treated allograft as compared with allografts from FK506-treated animals. In contrast, administration of FK506 significantly suppressed interferon (IFN)-γ but increased IL-10 expression as compared with that of SAHA-treated animals, and this effect was independent of SAHA. Interestingly, SAHA synergizes with FK506 to promote Foxp3 and CTLA4 expression. In vitro, SAHA reduced the proportion of Th17 cells in isolated CD4⁺ T-cell population and decreased expressions of IL-17A, IL-17F, STAT3 and RORγt in these cells. Moreover, SAHA enhances suppressive function of regulatory T (Treg) cells by upregulating the expression of CTLA-4 without affecting T effector cell proliferation, and increased the proportion of Treg by selectively promoting apoptosis of T effector cells. Therefore, SAHA, a HDACi, may be a promising immunosuppressive agent with potential benefit in conjunction with CNI drugs.
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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.