{"id":"doi:10.1016/j.isci.2026.117560","kind":"article","title":"Protective <i>IFIH1</i> variant reduces islet stress and dysfunction in a type 1 diabetes genetic background","authors":["Veronese-Paniagua DA","Banks C","Bradley K","Mukherjee N","Gale SE","Hinshaw KE","Meacham AM","Iwaloye OF","Tse HM","Mathews CE","Millman JR"],"author_count":11,"year":2026,"published":"2026-09-17","venue":"iScience","cited_by":0,"doi":"10.1016/j.isci.2026.117560","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.isci.2026.117560","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.isci.2026.117560","updated":null,"pmid":"42787837","pmcid":"PMC13602225","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13602225/pdf","abstract":"Genome-wide association studies have identified IFIH1 , which encodes the double-stranded RNA sensor MDA5, as a type 1 diabetes (T1D) risk locus. The IFIH1 E627∗ variant is associated with protection from T1D, whereas A946T is associated with increased risk. To examine how these variants influence islet responses to inflammatory and viral stress, we used CRISPR-Cas9 to engineer E627∗ or A946T into human pluripotent stem cells from a T1D donor and differentiated them into stem cell-derived islets (SC-islets). SC-islets were exposed to IFNα, poly(I:C), or coxsackievirus B3 and analyzed by single-cell RNA sequencing and functional assays. E627∗ SC-islets compared to A946T displayed reduced inflammatory and stress responses with lower apoptosis, viral burden, mitochondrial dysfunction, and insulin secretory impairment. These findings support a protective role for IFIH1 E627∗ in human islet responses to inflammatory and viral stress and provide insight into genetic mechanisms potentially linked to T1D pathogenesis.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Protective <i>IFIH1</i> variant reduces islet stress and dysfunction in a type 1 diabetes genetic background\" by Veronese-Paniagua DA, Banks C, Bradley K et al., https://doi.org/10.1016/j.isci.2026.117560, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-cell-therapy","name":"Gene & Cell Therapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}