PLX153898

GSE58998: The chromatin-modifying enzyme Ezh2 is a CD28-dependent molecule critical for the maintenance of Treg identity

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Regulatory T cells (Tregs) are essential for maintaining proper immune homeostasis. Extracellular signals (e.g. TCR, CD28, IL-2R) are necessary for the generation and maintenance of Tregs, but how these signals are integrated to control the gene expression patterns of Tregs is less clear. Here we show that the epigenetic regulator, Ezh2, was induced by CD28 costimulation and Ezh2 activity was elevated in Tregs as compared to conventional CD4+ T cells. Deletion of Ezh2 in mouse Tregs led to a progressive autoimmune disease because Tregs were compromised after activation, losing proper control of essential Treg lineage genes and adopting a gene expression pattern similar to Foxp3-deficient Tregs. Lineage-tracing of Ezh2-deficient Tregs in vivo confirmed that the cells were destabilized selectively in activated Treg populations, which led to a significant loss of Tregs in non-lymphoid tissues. These studies reveal an essential role for Ezh2 in the maintenance of Treg identity during cellular activation and differentiation. SOURCE: GAURAV CHOPRA (gchopra@diabetes.ucsf.edu) - BLUESTONE LAB UNIVERSITY OF CALIFORNIA - SAN FRANCISCO (UCSF)