ArticleEBioMedicine2018
PDL1 is expressed in the islets of people with type 1 diabetes and is up-regulated by interferons-α and-γ via IRF1 induction.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 4 of them syntheses that pooled it.
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Who cites it
130 citing papers in PubMed, 4 syntheses or guidelines pooled it, 181 citations in OpenAlex.
- PD-1 inhibitor-associated type 1 diabetes: A case report and systematic review.Frontiers in public health · 2022Pooled it
- Molecular Footprints of the Immune Assault on Pancreatic Beta Cells in Type 1 Diabetes.Frontiers in endocrinology · 2020Pooled it
- Pooled it
- Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review.European journal of endocrinology · 2019Pooled it
- Safety, Immune, and Antiviral Effects of Pegylated Interferon Alpha 2b Administration in Antiretroviral Therapy-Suppressed Individuals: Results of Pilot Clinical Trial.AIDS research and human retroviruses · 2021Trial
- The β-cells in type 1 diabetes mellitus: findings from human pancreas studies.Nature reviews. Endocrinology · 2026Review
- Article
- Cell-intrinsic functions of PD-L1 activate autophagy and prevent cytokine-induced apoptosis.Science advances · 2026Article
- Immune checkpoints and immunoregulation in metabolic diseases and cancers: pathological mechanisms and therapeutic potential.Signal transduction and targeted therapy · 2026Review
- Integrative gene target mapping, RNA sequencing, in silico molecular docking, ADMET profiling and molecular dynamics simulation study of marine derived molecules for type 1 diabetes mellitus.Molecular diversity · 2026Article
- Imaging mass cytometry reveals functional and immunological changes during type 1 diabetes progression in human pancreata.Nature metabolism · 2026Article
- A surviving beta cell subpopulation enriched in patients with T1D.bioRxiv : the preprint server for biology · 2026Article
- 3D imaging of an entire pancreas shows inverse proportions of extra-islet versus islet-associated β cells in late-onset type 1 diabetes.Science advances · 2026Article
- Unlocking beta cell health: The clinical potential of extracellular vesicles in type 1 diabetes.Clinical and translational medicine · 2026Review
- Beta cell-targeted PD-1 agonist inhibits cell-mediated autoimmunity in pancreas tissue slices.Science advances · 2026Article
- Review
- Pembrolizumab-induced type-1 diabetes mellitus: clinical characteristics, therapeutic strategies, and prognosis from a retrospective analysis of 43 published cases.Frontiers in endocrinology · 2026Article
- Immune Checkpoint Restoration as a Therapeutic Strategy to Halt Diabetes-Driven Atherosclerosis.Biology · 2025Review
- Small things matter: Lack of extraislet β cells in type 1 diabetes.Science advances · 2025Article
- Inhibition of cell-mediated immunity in type 1 diabetes by beta cell-targeted PD-1 agonists in pancreas tissue slices.bioRxiv : the preprint server for biology · 2025Article
70 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundAntibodies targeting PD-1 and its ligand PDL1 are used in cancer immunotherapy but may lead to autoimmune diseases, including type 1 diabetes (T1D). It remains unclear whether PDL1 is expressed in pancreatic islets of people with T1D and how is it regulated.
methodsThe expression of PDL1, IRF1, insulin and glucagon was evaluated in samples of T1D donors by immunofluorescence. Cytokine-induced PDL1 expression in the human beta cell line, EndoC-βH1, and in primary human pancreatic islets was determined by real-time RT-PCR, flow cytometry and Western blot. Specific and previously validated small interference RNAs were used to inhibit STAT1, STAT2, IRF1 and JAK1 signaling. Key results were validated using the JAK inhibitor Ruxolitinib.
findingsPDL1 was present in insulin-positive cells from twelve T1D individuals (6 living and 6 deceased donors) but absent from insulin-deficient islets or from the islets of six non-diabetic controls. Interferons-α and -γ, but not interleukin-1β, induced PDL1 expression in vitro in human islet cells and EndoC-βH1 cells. Silencing of STAT1 or STAT2 individually did not prevent interferon-α-induced PDL1, while blocking of JAKs - a proposed therapeutic strategy for T1D - or IRF1 prevented PDL1 induction.
interpretationThese findings indicate that PDL1 is expressed in beta cells from people with T1D, possibly to attenuate the autoimmune assault, and that it is induced by both type I and II interferons via IRF1.
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