GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE275nnn/GSE275045/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275045GEOGSEfalseEzh2 and intracellular Ca2+ signals interdependently coordinate GVHD and CAR T cell responses [RNA-seq_1]During graft-versus-host disease (GVHD), Ca2+ signals are crucial for the establishment of T cell alloim-munity, however, excessive or prolonged Ca2+ signals lead to T cell death and dysfunction. How alloreac-tive T cells regulate a delicate regulate intracellular Ca2+ response to induce GVHD remains poorly defined. We demonstrate that Ezh2 acts as Ca2+ signaling brake to limit excessive intracellular Ca2+ responses in activated T cells, thereby promoting survival of alloreactive T cells that mediate GVHD. Ezh2 loss resulted in enhanced intracellular Ca2+ responses and upregulation of gene programs that promote effector differen-tiation in activated T cells. Conditional deletion of Stim1 (which mediates cytosolic Ca2+ entry) synthetical-ly rescued antigen-activated non-viable Ezh2-null T cells and their capacity to induce GVHD. Ezh2 re-pressed the expression of endoplasmic reticulum Ca2+ release channel inositol 1,4,5-trisphosphate (InsP3) receptor 2 (Itpr2) to modulate intracellular Ca2+ responses. Deleting Itpr2 in Ezh2-null T cells reduced cy-tosolic Ca2+ entry, improved their capacity to mediate GVHD and eliminate leukemia in mice. Our findings identify that Ezh2 is a master regulator of Ca2+ signals in antigen-driven T cells. Furthermore, selectively heightening intracellular Ca2+ signals in alloreactive T cells may lead to new strategies to control GVHD.2026/07/08GSE275045GSM8464680GSM8464684GSM8464683GSM8464682GSM8464681GSM8464688GSM8464687GSM8464686GSM8464685GSM846467917021275045Mus musculus[42020715]