ArticleFrontiers in immunology2019
Inhibition of Cdk8/Cdk19 Activity Promotes Treg Cell Differentiation and Suppresses Autoimmune Diseases.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- A novel CDK8/19 inhibitor RO8323 mitigates allograft rejection through dual mechanisms of action to modulate regulatory T cell and myeloid cell.Acta pharmacologica Sinica · 2026Article
- Taming autoimmunity: Alpha-1 antitrypsin overexpressing mesenchymal stromal cells promote regulatory T cell crosstalk to reverse diabetes.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Anti-CD3 mAb treatment reshapes infiltrating T and β cells in the islets in autoimmune diabetes.JCI insight · 2026Article
- Therapeutic potential of CDK8 inhibitor combined with sorafenib for hepatocellular carcinoma: mechanistic insights and in vitro validation.European journal of medical research · 2026Article
- Mechanistic insights from experimental autoimmune encephalomyelitis into immune regulation, autophagy, gut microbiota, blood-brain barrier integrity, and NLRP3 inflammasome-mediated pyroptosis in multiple sclerosis: potential clinical implications.Frontiers in neuroscience · 2026Review
- The Role of CDKs in the Regulation of the Monocyte/Macrophage Immune Response.Current medicinal chemistry · 2026Review
- Assessment and Characterization of Induced Alloantigen-Specific Regulatory T Cells Obtained by the Inhibition of CDK8/19 with the AS2863619 Compound.International journal of molecular sciences · 2025Article
- Generation of Regulatory T Cells From Human Memory CD4European journal of immunology · 2025Article
- Mediator kinase inhibition drives myometrial stem cell differentiation and the uterine fibroid phenotype through super-enhancer reprogramming.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome.eLife · 2025Article
- Mediator kinase inhibition drives myometrial stem cell differentiation and the uterine fibroid phenotype through super-enhancer reprogramming.Research square · 2024Article
- Mediator kinase inhibition suppresses hyperactive interferon signaling in Down syndrome.bioRxiv : the preprint server for biology · 2024Article
- STING pathway as a cancer immunotherapy: Progress and challenges in activating anti-tumor immunity.Molecular biology reports · 2024Review
- Unveiling the impact of CDK8 on tumor progression: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2024Review
- Foxp3-mediated blockage of ryanodine receptor 2 underlies contact-based suppression by regulatory T cells.The Journal of clinical investigation · 2023Article
- CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins.Nucleic acids research · 2023Article
- Inhibition of Cyclin-Dependent Kinases 8/19 Restricts Bacterial and Virus-Induced Inflammatory Responses in Monocytes.Viruses · 2023Article
- Combining bioinformatics and machine learning to identify common mechanisms and biomarkers of chronic obstructive pulmonary disease and atrial fibrillation.Frontiers in cardiovascular medicine · 2023Article
- The role of the adaptive immune system and T cell dysfunction in neurodegenerative diseases.Journal of neuroinflammation · 2022Review
- Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Foxp3 expressing regulatory T (Treg) cells, as the central negative regulator of adaptive immune system, are essential to suppress immune response and maintain immune homeostasis. However, the function of Treg cells is frequently compromised in autoimmunity and hyper-activated in infections and tumor microenvironments. Thus, manipulating Treg cells becomes a promising therapeutic strategy for treating various diseases. Here we reported that inhibition of Cdk8/Cdk19 activity by small molecule inhibitors CCT251921 or Senexin A greatly promoted the differentiation of Treg cells and the expression of Treg signature genes, such as Foxp3, CTLA4, PD-1, and GITR. Mechanistically, we found that the augmented Treg cell differentiation was due to sensitized TGF-β signaling by Cdk8/Cdk19 inhibition, which was associated with attenuation of IFN-γ-Stat1 signaling and enhancement of phosphorylated Smad2/3. Importantly, treatment with Cdk8/Cdk19 inhibitor CCT251921 significantly increased Treg population and ameliorated autoimmune symptoms in an experimental autoimmune encephalomyelitis (EAE) model. Taken together, our study reveals a novel role of Cdk8/Cdk19 in Treg cell differentiation and provides a potential target for Treg cell based therapeutics.
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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.