GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE178nnn/GSE178492/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE178492GEOGSEfalseChromatin accessibility changes underlying progression from islet autoantibody positivity to type 1 diabetesType 1 diabetes (T1D) usually has a preclinical phase identified by the presence of circulating autoantibodies to pancreatic islet antigens, and most young children who have multiple autoantibodies progress to diabetes within 10 years. While autoantibodies denote underlying islet autoimmunity, how this process is initiated and then progresses to clinical diabetes on a background of genetic susceptibility is not clearly understood. Only one study has thus far reported changes in gene expression in isolated immune cells associated with progression to islet autoimmunity. We analysed gene expression and chromatin accessibility by ATAC-seq in CD4+ T cells in four genetically at-risk children with islet autoantibodies who progressed to diabetes in ≤ 3 years (‘progressors’), compared to five at-risk children matched for sex, age and HLA who had not progressed (‘non-progressors). In progressors, differentially expressed genes (DEGs) were enriched for cytotoxic genes/pathways and CD4+ TEMRA-like expression signatures. From ATAC-seq data, we generated the first map of chromatin accessibility in T cells of islet autoantibody-positive children. Progression was associated with a subtle reconfiguration of regulatory chromatin regions, and some of the chromatin conformation changes could be linked to progression associated expression changes at cytotoxic genes. In summary, our findings highlight a role for cytotoxic CD4+ T cells in progressive islet immunopathology, and suggest that some of the alterations in chromatin accessibility could underly progression associated gene expression changes2026/06/17GSE178492GSM5392768GSM5392767GSM5392769GSM5392764GSM5392763GSM5392766GSM5392765GSM5392770GSM539276218573178492Homo sapiens