ArticleJournal of autoimmunity2016
Inherent ER stress in pancreatic islet β cells causes self-recognition by autoreactive T cells in type 1 diabetes.
Article in Journal of autoimmunity, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 79 citations in OpenAlex.
- Beta Cell Stress to Epitope Diversification: Post-Translationally Modified Antigens in Type 1 Diabetes.Immunological reviews · 2026Review
- Oxidative Stress, Post-Translational Modifications, and Type 1 Diabetes Pathogenesis.Immunological reviews · 2026Review
- Beyond Sequence: Posttranslational Remodeling of Antigens in Autoimmunity.Immunological reviews · 2026Review
- Citrullination and Deamidation in Type 1 Diabetes: Linking Beta Cell Stress to Neoantigen-Driven Autoimmunity.Immunological reviews · 2026Review
- Beyond bystanders: How β cell stress shapes the autoimmune response in T1D.Science translational medicine · 2026Review
- Is the NOD mouse a good model for type 1 diabetes?Diabetologia · 2026Review
- Neoepitopes at the crossroads of immunometabolism: metabolic remodeling of antigen presentation in type 1 diabetes.Frontiers in immunology · 2026Review
- Stress-driven remodeling of antigen presentation and chemokine signaling in pancreatic β-cells: implications for type 1 diabetes.Frontiers in immunology · 2026Review
- Molecular and Inflammatory Etiologies of β-Cell Dysfunction in Type 1 Diabetes.Physiology (Bethesda, Md.) · 2025Review
- Immunopeptidome mining reveals a novel ERS-induced target in T1D.Cellular & molecular immunology · 2024Article
- The beta cell-immune cell interface in type 1 diabetes (T1D).Molecular metabolism · 2023Review
- Effects of multiple stressors on pancreatic human islets proteome reveal new insights into the pathways involved.Proteomics · 2023Article
- The Role of ER Stress in Diabetes: Exploring Pathological Mechanisms Using Wolfram Syndrome.International journal of molecular sciences · 2022Review
- IL-15 blockade and rapamycin rescue multifactorial loss of factor VIII from AAV-transduced hepatocytes in hemophilia A mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Setting the Stage for Insulin Granule Dysfunction during Type-1-Diabetes: Is ER Stress the Culprit?Biomedicines · 2022Review
- Posttranslational modifications in diabetes: Mechanisms and functions.Reviews in endocrine & metabolic disorders · 2022Review
- Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes.Cell reports · 2022Article
- Defective Proinsulin Handling Modulates the MHC I Bound Peptidome and Activates the Inflammasome in β-Cells.Biomedicines · 2022Article
- Environmental Triggering of Type 1 Diabetes Autoimmunity.Frontiers in endocrinology · 2022Review
- Aberrant expression of transglutaminase 2 in pancreas and thymus of NOD mice underscores the importance of deamidation in neoantigen generation.Frontiers in endocrinology · 2022Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic β cell destruction induced by islet reactive T cells that have escaped central tolerance. Many physiological and environmental triggers associated with T1D result in β cell endoplasmic reticulum (ER) stress and dysfunction, increasing the potential for abnormal post-translational modification (PTM) of proteins. We hypothesized that β cell ER stress induced by environmental and physiological conditions generates abnormally-modified proteins for the T1D autoimmune response. To test this hypothesis we exposed the murine CD4(+) diabetogenic BDC2.5 T cell clone to murine islets in which ER stress had been induced chemically (Thapsigargin). The BDC2.5 T cell IFNγ response to these cells was significantly increased compared to non-treated islets. This β cell ER stress increased activity of the calcium (Ca(2+))-dependent PTM enzyme tissue transglutaminase 2 (Tgase2), which was necessary for full stress-dependent immunogenicity. Indeed, BDC2.5 T cells responded more strongly to their antigen after its modification by Tgase2. Finally, exposure of non-antigenic murine insulinomas to chemical ER stress in vitro or physiological ER stress in vivo caused increased ER stress and Tgase2 activity, culminating in higher BDC2.5 responses. Thus, β cell ER stress induced by chemical and physiological triggers leads to β cell immunogenicity through Ca(2+)-dependent PTM. These findings elucidate a mechanism of how β cell proteins are modified and become immunogenic, and reveal a novel opportunity for preventing β cell recognition by autoreactive T cells.
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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.