ArticleDiabetes, obesity & metabolism2020
Preclinical evaluation of tyrosine kinase 2 inhibitors for human beta-cell protection in type 1 diabetes.
Article in Diabetes, obesity & metabolism, 2020. 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, 38 citations in OpenAlex.
- Article
- New and emerging therapies in type 1 diabetes mellitus.The Journal of clinical investigation · 2026Review
- Systematic common and rare variant association testing in 392,030 whole genomes inmedRxiv : the preprint server for health sciences · 2026Article
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice.EBioMedicine · 2025Article
- Janus kinase and signal transducer and activator of transcription inhibitors in type 1 diabetes and immune checkpoint-related diabetes: current status and future perspectives.Frontiers in immunology · 2025Review
- Review
- Targeting Protein Kinases to Protect Beta-Cell Function and Survival in Diabetes.International journal of molecular sciences · 2024Review
- Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice.bioRxiv : the preprint server for biology · 2024Article
- Article
- Islet cells in human type 1 diabetes: from recent advances to novel therapies - a symposium-based roadmap for future research.The Journal of endocrinology · 2023Review
- Pharmacological inhibitors of β-cell dysfunction and death as therapeutics for diabetes.Frontiers in endocrinology · 2023Review
- Deucravacitinib, a tyrosine kinase 2 pseudokinase inhibitor, protects human EndoC-βH1 β-cells against proinflammatory insults.Frontiers in immunology · 2023Article
- Therapeutic Strategies Targeting Pancreatic Islet β-Cell Proliferation, Regeneration, and Replacement.Endocrinology · 2022Article
- The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α.Nature communications · 2022Article
- Transcription and splicing regulation by NLRC5 shape the interferon response in human pancreatic β cells.Science advances · 2022Article
- Small-molecule discovery in the pancreatic beta cell.Current opinion in chemical biology · 2022Review
- Genetic overlap between type 1 diabetes and other autoimmune diseases.Seminars in immunopathology · 2022Review
- Review
- Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
aimType 1 diabetes (T1D) is a chronic autoimmune disease leading to progressive loss of pancreatic beta cells. Interferon (IFN)-α plays a critical role in the crosstalk between pancreatic beta cells and the immune system in early insulitis. In human beta cells IFNα signals through JAK1 and TYK2, leading to endoplasmic reticulum stress, inflammation and HLA class I overexpression. IFNα, acting synergistically with IL-1β, induces apoptosis. Polymorphisms in TYK2 that decrease its activity are associated with protection against T1D, and we hypothesized that pharmacological inhibitors that specifically target TYK2 could protect human beta cells against the deleterious effects of IFNα. MATERIALS AND
methodsTwo TYK2 inhibitors provided by Nimbus Lakshmi were tested in human insulin-producing EndoC-βH1 cells and human islets to evaluate their effect on IFNα signalling, beta-cell function and susceptibility to viral infection using RT-qPCR, western blot, immunofluorescence, ELISA and nuclear dyes.
resultsThe two TYK2 inhibitors tested prevented IFNα-induced human beta-cell gene expression in a dose-dependent manner. They also protected human islets against IFNα + IL-1β-induced apoptosis. Importantly, these inhibitors did not modify beta-cell function or their survival following infection with the potential diabetogenic coxsackieviruses CVB1 and CVB5.
conclusionsThe two TYK2 inhibitors tested inhibit the IFNα signalling pathway in human beta cells, decreasing its pro-inflammatory and pro-apoptotic effects without sensitizing the cells to viral infection. The preclinical findings could pave the way for future clinical trials with TYK2 inhibitors for the prevention and treatment of type 1 diabetes.
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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 Socratic graph.