ArticleJCI insight2018
Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
81 citing papers in PubMed, 213 citations in OpenAlex.
- Trial
- Ladarixin, an inhibitor of the interleukin-8 receptors CXCR1 and CXCR2, in new-onset type 1 diabetes: A multicentre, randomized, double-blind, placebo-controlled trial.Diabetes, obesity & metabolism · 2022Trial
- Transcriptomics of type 1 diabetes progression: a validation study in newly diagnosed patients.EBioMedicine · 2026Article
- In Vivo Imaging of the Innate Immune System in the Pancreas in New-Onset and Long-Standing Type 1 Diabetes.Diabetes, obesity & metabolism · 2026Article
- Neutrophils and neutrophil extracellular traps in diabetes mellitus and its complications: Mechanisms and therapeutic implications.iScience · 2026Review
- Review
- (TCRαβCells · 2025Review
- The pathophysiology, presentation and classification of Type 1 diabetes.Diabetes, obesity & metabolism · 2025Review
- NETosis: A key player in autoimmunity, COVID-19, and long COVID.Journal of translational autoimmunity · 2025Review
- Neutrophils in Type 1 Diabetes: Untangling the Intricate Web of Pathways and Hypothesis.Biomolecules · 2025Review
- Tissue Resident and Infiltrating Immune Cells: Their Influence on the Demise of Beta Cells in Type 1 Diabetes.Biomolecules · 2025Review
- Exploring Neutrophil Heterogeneity and Plasticity in Health and Disease.Biomedicines · 2025Review
- Review
- Immunotherapy-Based Strategies for Treatment of Type 1 Diabetes.Hormone research in paediatrics · 2025Review
- Effect of the autoimmune-associated genetic variantFrontiers in immunology · 2025Article
- Beyond inflammation: the multifaceted therapeutic potential of targeting the CXCL8-CXCR1/2 axis in type 1 diabetes.Frontiers in immunology · 2025Review
- Time to reframe the disease staging system for type 1 diabetes.The lancet. Diabetes & endocrinology · 2024Review
- Genetic relations between type 1 diabetes, coronary artery disease and leukocyte counts.Diabetologia · 2024Article
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
- Insulitis in human type 1 diabetes: lessons from an enigmatic lesion.European journal of endocrinology · 2024Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 8 institutions in 5 countries.
Funding
Abstract
backgroundNeutrophils and their inflammatory mediators are key pathogenic components in multiple autoimmune diseases, while their role in human type 1 diabetes (T1D), a disease that progresses sequentially through identifiable stages prior to the clinical onset, is not well understood. We previously reported that the number of circulating neutrophils is reduced in patients with T1D and in presymptomatic at-risk subjects. The aim of the present work was to identify possible changes in circulating and pancreas-residing neutrophils throughout the disease course to better elucidate neutrophil involvement in human T1D.
methodsData collected from 389 subjects at risk of developing T1D, and enrolled in 4 distinct studies performed by TrialNet, were analyzed with comprehensive statistical approaches to determine whether the number of circulating neutrophils correlates with pancreas function. To obtain a broad analysis of pancreas-infiltrating neutrophils throughout all disease stages, pancreas sections collected worldwide from 4 different cohorts (i.e., nPOD, DiViD, Siena, and Exeter) were analyzed by immunohistochemistry and immunofluorescence. Finally, circulating neutrophils were purified from unrelated nondiabetic subjects and donors at various T1D stages and their transcriptomic signature was determined by RNA sequencing.
resultsHere, we show that the decline in β cell function is greatest in individuals with the lowest peripheral neutrophil numbers. Neutrophils infiltrate the pancreas prior to the onset of symptoms and they continue to do so as the disease progresses. Of interest, a fraction of these pancreas-infiltrating neutrophils also extrudes neutrophil extracellular traps (NETs), suggesting a tissue-specific pathogenic role. Whole-transcriptome analysis of purified blood neutrophils revealed a unique molecular signature that is distinguished by an overabundance of IFN-associated genes; despite being healthy, said signature is already present in T1D-autoantibody-negative at-risk subjects.
conclusionsThese results reveal an unexpected abnormality in neutrophil disposition both in the circulation and in the pancreas of presymptomatic and symptomatic T1D subjects, implying that targeting neutrophils might represent a previously unrecognized therapeutic modality.
fundingJuvenile Diabetes Research Foundation (JDRF), NIH, Diabetes UK.
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Registered trials
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.