tRNA-derived fragments in T lymphocyte-beta cell crosstalk and in type 1 diabetes pathogenesis in NOD mice.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38967669", "kind": "science-record", "revision": 4, "content_hash": "sha256:db43a4f9c1589163b90f52d99fa1b525c822e314bcd3b3683bbb68212838ece4", "created_at": "2026-11-01T20:29:02Z", "updated_at": "2026-11-01T22:54:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "tRNA-derived fragments in T lymphocyte-beta cell crosstalk and in type 1 diabetes pathogenesis in NOD mice.", "doi": "10.1007/s00125-024-06207-3", "pmid": "38967669", "authors": ["Flora Brozzi", "Cécile Jacovetti", "Cristina Cosentino", "Véronique Menoud", "Kejing Wu", "Mustafa Bilal Bayazit", "Baroj Abdulkarim", "Christian Iseli", "Nicolas Guex", "Claudiane Guay", "Romano Regazzi"], "journal": "Diabetologia", "year": 2024, "abstract": "AIMS/HYPOTHESIS: tRNAs play a central role in protein synthesis. Besides this canonical function, they were recently found to generate non-coding RNA fragments (tRFs) regulating different cellular activities. The aim of this study was to assess the involvement of tRFs in the crosstalk between immune cells and beta cells and to investigate their contribution to the development of type 1 diabetes.\nMETHODS: Global profiling of the tRFs present in pancreatic islets of 4- and 8-week-old NOD mice and in extracellular vesicles released by activated CD4+ T lymphocytes was performed by small RNA-seq. Changes in the level of specific fragments were confirmed by quantitative PCR. The transfer of tRFs from immune cells to beta cells occurring during insulitis was assessed using an RNA-tagging approach. The functional role of tRFs increasing in beta cells during the initial phases of type 1 diabetes was determined by overexpressing them in dissociated islet cells and by determining the impact on gene expression and beta cell apoptosis.\nRESULTS: We found that the tRF pool was altered in the islets of NOD mice during the initial phases of type 1 diabetes. Part of these changes were triggered by prolonged exposure of beta cells to proinflammatory cytokines (IL-1β, TNF-α and IFN-γ) while others resulted from the delivery of tRFs produced by CD4+ T lymphocytes infiltrating the islets. Indeed, we identified several tRFs that were enriched in extracellular vesicles from CD4+/CD25- T cells and were transferred to beta cells upon adoptive transfer of these immune cells in NOD.SCID mice. The tRFs delivered to beta cells during the autoimmune reaction triggered gene expression changes that affected the immune regulatory capacity of insulin-secreting cells and rendered the cells more prone to apoptosis.\nCONCLUSIONS/INTERPRETATION: Our data point to tRFs as novel players in the crosstalk between the immune system and insulin-secreting cells and suggest a potential involvement of this novel class of non-coding RNAs in type 1 diabetes pathogenesis.\nDATA AVAILABILITY: Sequences are available from the Gene Expression Omnibus (GEO) with accession numbers GSE242568 and GSE256343.", "claims": [{"id": "claim-method", "statement": "For each tRF, p values and false discovery rates (FDRs) were obtained based on the model of negative binomial distribution. No data were excluded from the study and no randomisation was carried out. Data are presented as the mean ± SD. A two-tailed one-sample t test was used to compare datasets to a control value settled to 1, and two-tailed paired or unpaired t tests were used for comparing two datasets. One- or two-way ANOVA followed by Dunnett or Sidàk post hoc tests were used to compare multiple datasets. Correlation of datasets was assessed by a two-tailed Pearson test. Differences between datasets were considered significant when the p value was <0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38967669", "locator": "sections[10] \"tRF annotation and analysis\" paragraph 3", "quote": "For each tRF, p values and false discovery rates (FDRs) were obtained based on the model of negative binomial distribution."}, {"asset": "source:pmid:38967669", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "No data were excluded from the study and no randomisation was carried out."}, {"asset": "source:pmid:38967669", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "Data are presented as the mean ± SD."}, {"asset": "source:pmid:38967669", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "A two-tailed one-sample t test was used to compare datasets to a control value settled to 1, and two-tailed paired or unpaired t tests were used for comparing two datasets."}, {"asset": "source:pmid:38967669", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "One- or two-way ANOVA followed by Dunnett or Sidàk post hoc tests were used to compare multiple datasets."}, {"asset": "source:pmid:38967669", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "Correlation of datasets was assessed by a two-tailed Pearson test."}, {"asset": "source:pmid:38967669", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "Differences between datasets were considered significant when the p value was <0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Sequence data are available from the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) with accession numbers GSE242568 and GSE256343.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38967669", "locator": "sections[30] \"notes\" paragraph 1", "quote": "Sequence data are available from the Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) with accession numbers GSE242568 and GSE256343."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We found that the tRF pool was altered in the islets of NOD mice during the initial phases of type 1 diabetes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38967669", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We found that the tRF pool was altered in the islets of NOD mice during the initial phases of type 1 diabetes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We found that the tRF pool was altered in the islets of NOD mice during the initial phases of 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:38967669"], "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. 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Changes in the level of specific fragments", ") were housed under a 12 h light–dark cycle. RNA-seq analysis of pulled-down EU-tagged RNA We wro"], "order_basis": "paper_text_order:653", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["the impact on gene expression and beta cell apoptosis. RESULTS: We found that the tRF pool was alt", "g cells and rendered the cells more prone to apoptosis. CONCLUSIONS/INTERPRETATION: Our data point"], "order_basis": "paper_text_order:1092", "id": "assay:2"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["For each tRF, p values and false discovery rates (FDRs) were obtained based on the model of negative binomial distribution. No data were excluded from the study and no randomisation was carried out. Data are presented as the mean ± SD. A two-tailed one-sample t test was used to compare datasets to a control value settled to 1, and two-tailed paired or unpaired t tests were used for comparing two datasets. One- or two-way ANOVA followed by Dunnett or Sidàk post hoc tests were used to compare multiple datasets. 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