ArticleDiabetes2015
PD-L1-driven tolerance protects neurogenin3-induced islet neogenesis to reverse established type 1 diabetes in NOD mice.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients.The Journal of clinical investigation · 2015Trial
- Nanomedicine targeting the PD-1/PD-L1 axis in autoimmune diseases: breaking conventional barriers to restore immune tolerance.Journal of nanobiotechnology · 2025Review
- From Edmonton to Lantidra and beyond: immunoengineering islet transplantation to cure type 1 diabetes.Frontiers in transplantation · 2025Review
- Islet allografts expressing a PD-L1 and IDO fusion protein evade immune rejection and reverse preexisting diabetes in immunocompetent mice without systemic immunosuppression.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Changes of macrophage and CD4Scientific reports · 2022Article
- Engineered immunomodulatory accessory cells improve experimental allogeneic islet transplantation without immunosuppression.Science advances · 2022Article
- Syngeneically transplanted insulin producing cells differentiated from adipose derived stem cells undergo delayed damage by autoimmune responses in NOD mice.Scientific reports · 2022Article
- Current Topics of Relevance to the Xenotransplantation of Free Pig Islets.Frontiers in immunology · 2022Review
- The Role of Programmed Death-1 in Type 1 Diabetes.Current diabetes reports · 2021Review
- Novel human immunomodulatory T cell receptors and their double-edged potential in autoimmunity, cardiovascular disease and cancer.Cellular & molecular immunology · 2021Review
- A Stem Cell Approach to Cure Type 1 Diabetes.Cold Spring Harbor perspectives in biology · 2021Review
- Immunotherapy via PD-L1-presenting biomaterials leads to long-term islet graft survival.Science advances · 2020Article
- Type 1 diabetes pathogenesis and the role of inhibitory receptors in islet tolerance.Annals of the New York Academy of Sciences · 2020Review
- PDL1 is expressed in the islets of people with type 1 diabetes and is up-regulated by interferons-α and-γ via IRF1 induction.EBioMedicine · 2018Article
- CD4 T Cells Reactive to Hybrid Insulin Peptides Are Indicators of Disease Activity in the NOD Mouse.Diabetes · 2018Article
- Anti-TCRβ mAb in Combination With Neurogenin3 Gene Therapy Reverses Established Overt Type 1 Diabetes in Female NOD Mice.Endocrinology · 2017Article
- Targeting memory T cells in type 1 diabetes.Current diabetes reports · 2015Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors.
Funding
Abstract
A breakdown in self-tolerance underlies autoimmune destruction of β-cells and type 1 diabetes. A cure by restoring β-cell mass is limited by the availability of transplantable β-cells and the need for chronic immunosuppression. Evidence indicates that inhibiting costimulation through the PD-1/PD-L1 pathway is central to immune tolerance. We therefore tested whether induction of islet neogenesis in the liver, protected by PD-L1-driven tolerance, reverses diabetes in NOD mice. We demonstrated a robust induction of neo-islets in the liver of diabetic NOD mice by gene transfer of Neurogenin3, the islet-defining factor, along with betacellulin, an islet growth factor. These neo-islets expressed all the major pancreatic hormones and transcription factors. However, an enduring restoration of glucose-stimulated insulin secretion and euglycemia occurs only when tolerance is also induced by the targeted overexpression of PD-L1 in the neo-islets, which results in inhibition of proliferation and increased apoptosis of infiltrating CD4(+) T cells. Further analysis revealed an inhibition of cytokine production from lymphocytes isolated from the liver but not from the spleen of treated mice, indicating that treatment did not result in generalized immunosuppression. This treatment strategy leads to persistence of functional neo-islets that resist autoimmune destruction and consequently an enduring reversal of diabetes in NOD mice.
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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.