ArticleDiabetes2011
Peripheral and islet interleukin-17 pathway activation characterizes human autoimmune diabetes and promotes cytokine-mediated β-cell death.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 212 citations in OpenAlex.
- Clinical parameters and emerging biomarkers of partial remission in pediatric type 1 diabetes: a systematic review.Frontiers in endocrinology · 2026Pooled it
- Ustekinumab for type 1 diabetes in adolescents: a multicenter, double-blind, randomized phase 2 trial.Nature medicine · 2024Trial
- Associations Between Serum Fatty Acids and Immunological Markers in Children Developing Islet Autoimmunity-The TRIGR Nested Case-Control Study.Frontiers in immunology · 2022Trial
- Trial
- Treg gene signatures predict and measure type 1 diabetes trajectory.JCI insight · 2019Trial
- Changes in T-cell subsets identify responders to FcR-nonbinding anti-CD3 mAb (teplizumab) in patients with type 1 diabetes.European journal of immunology · 2016Trial
- Article
- Type 1 Diabetes: A Guide to Autoimmune Mechanisms for Clinicians.Diabetes, obesity & metabolism · 2025Review
- T helper 17 cells and interleukin-17 immunity in type 1 diabetes: From pathophysiology to targeted immunotherapies.World journal of diabetes · 2025Review
- Type 1 Diabetes/Hidradenitis Suppurativa Comorbidity-A Population-Based Study.Journal of clinical medicine · 2025Article
- Insulin Secretion and Insulin Sensitivity Change in Different Stages of Adult-Onset Type 1 Diabetes: A Cross-Sectional Study.Journal of clinical medicine · 2025Article
- Immunotherapies for prevention and treatment of type 1 diabetes.Immunotherapy · 2025Review
- Extracellular(Serum) Levels of Matrix Metalloproteinases in Pediatric Type 1 Diabetes Mellitus and Association with Diabetic Ketoacidosis and Cerebral Edema.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- IL17RA and IL21R polymorphisms influence type 1 diabetes predisposition and autoimmune phenotypes.Frontiers in endocrinology · 2025Article
- The relationship between schizophrenia or schizoaffective disorder and type 1 diabetes mellitus: a scoping review of observational studies.Neuropsychiatrie : Klinik, Diagnostik, Therapie und Rehabilitation : Organ der Gesellschaft Osterreichischer Nervenarzte und Psychiater · 2024Article
- Impact of hyperglycemia on immune cell function: a comprehensive review.Diabetology international · 2024Review
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
- Shared and distinct genetics of pure type 1 diabetes and type 1 diabetes with celiac disease, homology in their auto-antigens and immune dysregulation states: a study from North India.Acta diabetologica · 2024Article
- Distinct cellular immune responses in children en route to type 1 diabetes with different first-appearing autoantibodies.Nature communications · 2024Article
- Mechanisms underlying the development of type 1 diabetes in ART-treated people living with HIV: an enigmatic puzzle.Frontiers in immunology · 2024Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 4 countries.
Funding
Abstract
objectiveCD4 T-cells secreting interleukin (IL)-17 are implicated in several human autoimmune diseases, but their role in type 1 diabetes has not been defined. To address the relevance of such cells, we examined IL-17 secretion in response to β-cell autoantigens, IL-17A gene expression in islets, and the potential functional consequences of IL-17 release for β-cells. RESEARCH DESIGN AND
methodsPeripheral blood CD4 T-cell responses to β-cell autoantigens (proinsulin, insulinoma-associated protein, and GAD65 peptides) were measured by IL-17 enzyme-linked immunospot assay in patients with new-onset type 1 diabetes (n = 50). mRNA expression of IL-17A and IFNG pathway genes was studied by qRT-PCR using islets obtained from subjects who died 5 days and 10 years after diagnosis of disease, respectively, and from matched control subjects. IL-17 effects on the function of human islets, rat β-cells, and the rat insulinoma cell line INS-1E were examined.
resultsA total of 27 patients (54%) showed IL-17 reactivity to one or more β-cell peptides versus 3 of 30 (10%) control subjects (P = 0.0001). In a single case examined close to diagnosis, islet expression of IL17A, RORC, and IL22 was detected. It is noteworthy that we show that IL-17 mediates significant and reproducible enhancement of IL-1β/interferon (IFN)-γ-induced and tumor necrosis factor (TNF)-α/IFN-γ-induced apoptosis in human islets, rat β-cells, and INS-1E cells, in association with significant upregulation of β-cell IL17RA expression via activation of the transcription factors STAT1 and nuclear factor (NF)-κB.
conclusionsCirculating IL-17(+) β-cell-specific autoreactive CD4 T-cells are a feature of type 1 diabetes diagnosis. We disclose a novel pathway to β-cell death involving IL-17 and STAT1 and NF-κB, rendering this cytokine a novel disease biomarker and potential therapeutic target.
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