Effect of deletion of UTX expression in NY8.3 progenitor CD8+ T cells

Type 1 diabetes (T1D) is a chronic autoimmune disease resulting from the destruction of insulin-producing beta cells. This persistence is due to the continual replenishment of short-live effector CD8+ T cells (autoimmune mediators, Tmed) in the pancreatic lymph nodes (pLNs) by a long-lived reservoir of stem-like memory CD8+ T cells (autoimmune progenitors, Tprog). We are investigating an epigenetic regulator UTX playing the role in Tprog to Tmed conversion. The NOD mice with T cell-specific UTX deficiency (UTXTCD mice) were protected from T1D. In addition, the deletion of UTX in CD8+ T cells resulted in the accumulation of Tprog and loss of Tmed populations in pLNs. The function of UTX is to demethylate the histone mark, H3K27 tri-methylation, leading to the open chromatin accessibility for gene expression. ATAC-seq and RNA-seq of antigen specific Tprog cells revealed a role of UTX in closing chromatin at progenitor gene loci while enforcing accessibility at effector gene loci. Taken together, these findings point to the potential of targeting UTX-mediated conversion of Tprog into Tmed for interrupting the T1D autoimmune response. To investigate the gene expression and chromatin accessibility regulated by UTX, we sorted the Ly108+CXCR6- CD8+ T cells harvested from pancreatic lymph node of NOD.NY8.3 (NY8.3) mice and T cell specific deletion UTX deficient NY8.3 mice (UTXTCD.NY8.3). We then perform gene expression profiling using RNA-seq and ATAC-seq. There are 3 samples for each group (NY8.3 and UTXTCD.NY8.3)