ArticleDiabetologia2009
Interferon regulatory factor-1 is a key transcription factor in murine beta cells under immune attack.
Article in Diabetologia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- A surviving beta cell subpopulation enriched in patients with T1D.bioRxiv : the preprint server for biology · 2026Article
- Coxsackievirus B infection invokes unique cell-type-specific responses in primary human pancreatic islets.Cell reports · 2025Article
- Integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D-associated genes and regulatory signals.Cell reports · 2025Article
- Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines.Cell genomics · 2022Article
- CpGmotifs: a tool to discover DNA motifs associated to CpG methylation events.BMC bioinformatics · 2021Article
- Large-scale association analyses identify host factors influencing human gut microbiome composition.Nature genetics · 2021Article
- Good Cop, Bad Cop: The Opposing Effects of Macrophage Activation State on Maintaining or Damaging Functional β-Cell Mass.Metabolites · 2020Review
- Genetic variants in glutamate cysteine ligase confer protection against type 2 diabetes.Molecular biology reports · 2020Article
- An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells.Nature communications · 2020Article
- Disruption of Monocyte and Macrophage Homeostasis in Periodontitis.Frontiers in immunology · 2020Article
- IL-17A increases the expression of proinflammatory chemokines in human pancreatic islets.Diabetologia · 2014Article
- Islet infiltration, cytokine expression and beta cell death in the NOD mouse, BB rat, Komeda rat, LEW.1AR1-iddm rat and humans with type 1 diabetes.Diabetologia · 2014Article
- High glucose induces CCL20 in proximal tubular cells via activation of the KCa3.1 channel.PloS one · 2014Article
- Type 1 diabetes: translating mechanistic observations into effective clinical outcomes.Nature reviews. Immunology · 2013Review
- STAT1 is a master regulator of pancreatic {beta}-cell apoptosis and islet inflammation.The Journal of biological chemistry · 2011Article
- Current status of immunomodulatory and cellular therapies in preclinical and clinical islet transplantation.Journal of transplantation · 2011Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIFN-gamma, together with other inflammatory cytokines such as IL-1beta and TNF-alpha, contributes to beta cell death in type 1 diabetes. We analysed the role of the transcription factor interferon regulatory factor (IRF)-1, a downstream target of IFN-gamma/signal transducer and activator of transcription (STAT)-1, in immune-mediated beta cell destruction.
methodsIslets from mice lacking Irf-1 (Irf-1 (-/-)) and control C57BL/6 mice were transplanted in overtly diabetic NOD mice. Viability and functionality of islets were evaluated in vitro. Chemokine expression by Irf-1 (-/-) islets and INS-1E cells transfected with Irf-1 short interfering RNA (siRNA) was measured by real-time PCR as well as in functional assays in vitro.
resultsIRF-1 deletion in islets was associated with higher prevalence of primary non-function (63% vs 25%, p <or= 0.05) and shorter functioning graft survival (6.0 +/- 2.6 vs 10.4 +/- 4.8 days, p <or= 0.05) in contrast to similar skin graft survival. Although Irf-1 (-/-) islets were resistant to cytokine-induced cell death, insulin secretion by them was lower than that of control C57BL/6 islets under medium and cytokine conditions. IL-1 receptor antagonist partly restored the cytokine-induced secretory defect in vitro and completely prevented primary non-function in vivo. Cytokine-exposed Irf-1 (-/-) islets and INS-1E cells transfected with Irf-1 siRNA showed increased expression of Mcp-1 (also known as Ccl2), Ip-10 (also known as Cxcl10), Mip-3alpha (also known as Ccl20) and Inos (also known as Nos2) mRNA and elevated production of monocyte chemoattractant protein-1 (MCP-1) and nitrite compared with controls. In vivo, Irf-1 (-/-) islets displayed a higher potential to attract immune cells, reflected by more aggressive immune infiltration in the grafted islets. CONCLUSIONS/
interpretationThese data indicate a key regulatory role for IRF-1 in insulin and chemokine secretion by pancreatic islets under inflammatory attack.
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