Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32500289", "kind": "science-record", "revision": 5, "content_hash": "sha256:0b57af47e6a1d79d45832b360fe4511114ef4d340868af5e0a8cf20ac7b1bc91", "created_at": "2026-11-01T17:33:44Z", "updated_at": "2026-11-01T22:44:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes.", "doi": "10.1007/s00125-020-05179-4", "pmid": "32500289", "authors": ["Kameron B Rodrigues", "Matthew J Dufort", "Alba Llibre", "Cate Speake", "M Jubayer Rahman", "Vincent Bondet", "Juan Quiel", "Peter S Linsley", "Carla J Greenbaum", "Darragh Duffy", "Kristin V Tarbell"], "journal": "Diabetologia", "year": 2020, "abstract": "AIMS/HYPOTHESIS: Self-antigen-specific T cell responses drive type 1 diabetes pathogenesis, but alterations in innate immune responses are also critical and not as well understood. Innate immunity in human type 1 diabetes has primarily been assessed via gene-expression analysis of unstimulated peripheral blood mononuclear cells, without the immune activation that could amplify disease-associated signals. Increased responsiveness in each of the two main innate immune pathways, driven by either type 1 IFN (IFN-1) or IL-1, have been detected in type 1 diabetes, but the dominant innate pathway is still unclear. This study aimed to determine the key innate pathway in type 1 diabetes and assess the whole blood immune stimulation assay as a tool to investigate this.\nMETHODS: The TruCulture whole blood ex vivo stimulation assay, paired with gene expression and cytokine measurements, was used to characterise changes in the stimulated innate immune response in type 1 diabetes. We applied specific cytokine-induced signatures to our data, pre-defined from the same assays measured in a separate cohort of healthy individuals. In addition, NOD mice were stimulated with CpG and monocyte gene expression was measured.\nRESULTS: Monocytes from NOD mice showed lower baseline vs diabetes-resistant B6.g7 mice, but higher induced IFN-1-associated gene expression. In human participants, ex vivo whole blood stimulation revealed higher induced IFN-1 responses in type 1 diabetes, as compared with healthy control participants. In contrast, neither the IL-1-induced gene signature nor response to the adaptive immune stimulant Staphylococcal enterotoxin B were significantly altered in type 1 diabetes samples vs healthy control participants. Targeted gene-expression analysis showed that this enhanced IFN response was specific to IFN-1, as IFN-γ-driven responses were not significantly different.\nCONCLUSIONS/INTERPRETATION: Our study identifies increased responsiveness to IFN-1 as a feature of both the NOD mouse model of autoimmune diabetes and human established type 1 diabetes. A stimulated IFN-1 gene signature may be a potential biomarker for type 1 diabetes and used to evaluate the effects of therapies targeting this pathway.\nDATA AVAILABILITY: Mouse gene expression data are found in the gene expression omnibus (GEO) repository, accession GSE146452 ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146452 ). Nanostring count data from the human experiments were deposited in the GEO repository, accession GSE146338 ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146338 ). Data files and R code for all analyses are available at https://github.com/rodriguesk/T1D_truculture_diabetologia . Graphical abstract.", "claims": [{"id": "claim-method", "statement": "Differential gene expression was determined using limma-voom [42], accounting for non-independence of samples from the same participant using limma’s duplicateCorrelation. 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Data files and R code for all analyses are available at https://github.com/rodriguesk/T1D_truculture_diabetologia."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our study identifies increased responsiveness to IFN-1 as a feature of both the NOD mouse model of autoimmune diabetes and human established type 1 diabetes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:32500289", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our study identifies increased responsiveness to IFN-1 as a feature of both the NOD mouse model of autoimmune diabetes and human established type 1 diabetes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our study identifies increased responsiveness to IFN-1 as a feature of both the NOD mouse model of autoimmune diabetes and human established type 1 diabetes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32500289"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE146338"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"fdr_threshold": "and Benjamini–Hochberg false discovery rate adjustment"}, "inputs": ["data:geo:GSE146338"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32500289", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s00125-020-05179-4", "sha256": "sha256:e342f110bbfc39b61fd2c920084abd429f45643b445e0183e4bb68ceeca7fd95", "bytes": 35012, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s00125-020-05179-4", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10091865", "source": "ncbi_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE146338", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146338", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE146338", "version": null, "note": "Mouse gene expression data are found in the gene expression omnibus (GEO) repository, accession GSE146452 (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE146452). 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