ArticleJCI insight2019
Epigenetic modulation of β cells by interferon-α via PNPT1/mir-26a/TET2 triggers autoimmune diabetes.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells.Frontiers in cell and developmental biology · 2020Pooled it
- Methylation and polygenic risk scores capture different features of Systemic Lupus Erythematosus.Rheumatology (Oxford, England) · 2026Article
- TET2: a critical regulatory hub with broad therapeutic implications across human diseases.Frontiers in immunology · 2026Review
- Recurrent single-CpG methylation differences and incomplete segregation in familial type 1 diabetes.Frontiers in immunology · 2026Article
- Environmental Mechanisms Influencing the Pathogenesis and Progression of Type 1 Diabetes.International journal of molecular sciences · 2025Review
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- MBD2 promotes B cell differentiation and BCR signaling in systemic lupus erythematosus by regulating the LEF-1-PTEN-PI3K axis.Cell death & disease · 2025Article
- Endogenous IL-22 contributes to the pathogenesis of salivary gland dysfunction in the non-obese diabetic model of Sjögren's syndrome.Molecular immunology · 2024Article
- Causal Effects of Oxidative Stress on Diabetes Mellitus and Microvascular Complications: Insights Integrating Genome-Wide Mendelian Randomization, DNA Methylation, and Proteome.Antioxidants (Basel, Switzerland) · 2024Article
- Role of IFN-α in Rheumatoid Arthritis.Current rheumatology reports · 2024Review
- Characterization of global research hotspots and trends on ten-eleven translocation 2: visualization and bibliometric analysis.American journal of translational research · 2022Article
- The behavior and functions of embryonic microglia.Anatomical science international · 2022Review
- Tet2 Controls the Responses of β cells to Inflammation in Autoimmune Diabetes.Nature communications · 2021Article
- Genome-wide association study identifies five risk loci for pernicious anemia.Nature communications · 2021Article
- The function and regulation of TET2 in innate immunity and inflammation.Protein & cell · 2021Review
- DNA Methylation Patterning and the Regulation of Beta Cell Homeostasis.Frontiers in endocrinology · 2021Review
- Molecular Mechanisms of Nutrient-Mediated Regulation of MicroRNAs in Pancreatic β-cells.Frontiers in endocrinology · 2021Review
- Role of Tet2 in Regulating Adaptive and Innate Immunity.Frontiers in cell and developmental biology · 2021Review
- Type 1 Diabetes: Interferons and the Aftermath of Pancreatic Beta-Cell Enteroviral Infection.Microorganisms · 2020Review
- Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells.JCI insight · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Type 1 diabetes (T1D) is caused by autoimmune destruction of pancreatic β cells. Mounting evidence supports a central role for β cell alterations in triggering the activation of self-reactive T cells in T1D. However, the early deleterious events that occur in β cells, underpinning islet autoimmunity, are not known. We hypothesized that epigenetic modifications induced in β cells by inflammatory mediators play a key role in initiating the autoimmune response. We analyzed DNA methylation (DNAm) patterns and gene expression in human islets exposed to IFN-α, a cytokine associated with T1D development. We found that IFN-α triggers DNA demethylation and increases expression of genes controlling inflammatory and immune pathways. We then demonstrated that DNA demethylation was caused by upregulation of the exoribonuclease, PNPase old-35 (PNPT1), which caused degradation of miR-26a. This in turn promoted the upregulation of ten-eleven translocation 2 (TET2) enzyme and increased 5-hydroxymethylcytosine levels in human islets and pancreatic β cells. Moreover, we showed that specific IFN-α expression in the β cells of IFNα-INS1CreERT2 transgenic mice led to development of T1D that was preceded by increased islet DNA hydroxymethylation through a PNPT1/TET2-dependent mechanism. Our results suggest a new mechanism through which IFN-α regulates DNAm in β cells, leading to changes in expression of genes in inflammatory and immune pathways that can initiate islet autoimmunity in T1D.
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