IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37581620", "kind": "science-record", "revision": 4, "content_hash": "sha256:e895e22083758b8bae5ac34c76b40b52046721803b625a2e8768b10466c372f0", "created_at": "2026-11-01T19:02:22Z", "updated_at": "2026-11-01T22:10:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity.", "doi": "10.1007/s00125-023-05991-8", "pmid": "37581620", "authors": ["Sofia Thomaidou", "Amadeo Munoz Garcia", "Sabine de Lange", "Jin Gan", "Arno R van der Slik", "Rob C Hoeben", "Bart O Roep", "Françoise Carlotti", "Arnaud Zaldumbide"], "journal": "Diabetologia", "year": 2023, "abstract": "AIMS/HYPOTHESIS: The inflammatory milieu characteristic of insulitis affects translation fidelity and generates defective ribosomal products (DRiPs) that participate in autoimmune beta cell destruction in type 1 diabetes. Here, we studied the role of early innate cytokines (IFNα) and late immune adaptive events (IFNɣ) in insulin DRiP-derived peptide presentation to diabetogenic CD8+ T cells.\nMETHODS: Single-cell transcriptomics of human pancreatic islets was used to study the composition of the (immuno)proteasome. Specific inhibition of the immunoproteasome catalytic subunits was achieved using siRNA, and antigenic peptide presentation at the cell surface of the human beta cell line EndoC-βH1 was monitored using peptide-specific CD8 T cells.\nRESULTS: We found that IFNγ induces the expression of the PSMB10 transcript encoding the β2i catalytic subunit of the immunoproteasome in endocrine beta cells, revealing a critical role in insulin DRiP-derived peptide presentation to T cells. Moreover, we showed that PSMB10 is upregulated in a beta cell subset that is preferentially destroyed in the pancreases of individuals with type 1 diabetes.\nCONCLUSIONS/INTERPRETATION: Our data highlight the role of the degradation machinery in beta cell immunogenicity and emphasise the need for evaluation of targeted immunoproteasome inhibitors to limit beta cell destruction in type 1 diabetes.\nDATA AVAILABILITY: The single-cell RNA-seq dataset is available from the Gene Expression Omnibus (GEO) using the accession number GSE218316 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218316 ).", "claims": [{"id": "claim-method", "statement": "Differential gene expression analysis was performed using the Wilcoxon rank sum test to analyse gene expression differences between treated and untreated cell groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37581620", "locator": "sections[9] \"RNA-seq data processing and analysis\" paragraph 2", "quote": "Differential gene expression analysis was performed using the Wilcoxon rank sum test to analyse gene expression differences between treated and untreated cell groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The single-cell RNA-seq dataset is available from the Gene Expression Omnibus (GEO) using the accession number GSE218316 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218316). All data are available in the main text or the electronic supplementary material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37581620", "locator": "sections[20] \"Data availability\" paragraph 2", "quote": "The single-cell RNA-seq dataset is available from the Gene Expression Omnibus (GEO) using the accession number GSE218316 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218316). All data are available in the main text or the electronic supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "IFNγ induces PSMB10 expression in endocrine beta cells, revealing a critical role for the β2i catalytic subunit of the immunoproteasome in insulin DRiP-derived peptide presentation to T cells.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37581620", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We found that IFNγ induces the expression of the PSMB10 transcript encoding the β2i catalytic subunit of the immunoproteasome in endocrine beta cells, revealing a critical role in insulin DRiP-derived peptide presentation to T cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "IFNγ induces PSMB10 expression in endocrine beta cells, revealing a critical role for the β2i catalytic subunit of the immunoproteasome in insulin DRiP-derived peptide presentation to T cells.", "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:37581620"], "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:GSE218316"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE218316"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37581620", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s00125-023-05991-8", "sha256": "sha256:b736d64354629d702dd7b8d2e4745a51c72900619f19ec8cc5aee3d96e0b4881", "bytes": 44025, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s00125-023-05991-8", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10542729", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE218316", "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=GSE218316", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE218316", "version": null, "note": "The single-cell RNA-seq dataset is available from the Gene Expression Omnibus (GEO) using the accession number GSE218316 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218316). 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE218316"], "resolved_accessions": ["GSE218316"], "statements": ["The single-cell RNA-seq dataset is available from the Gene Expression Omnibus (GEO) using the accession number GSE218316 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218316). All data are available in the main text or the electronic supplementary material."], "basis": "The paper names GSE218316 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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