Modulating Cholesterol Homeostasis to Build a Better T Cell Yoko Kidani, Steven J. Bensinger  Cell Metabolism  Volume 23, Issue 6, Pages 963-964 (June 2016) DOI: 10.1016/j.cmet.2016.05.015 Copyright © 2016 Elsevier Inc. Terms and Conditions

Figure 1 ACAT1 Modulates Cholesterol Levels in CD8 T Cells to Increase CTL Function (A) Upon antigen activation, T cells rapidly increase cholesterol synthesis through increased transcriptional activity of SREBPs. De novo synthesized or imported cholesterol is further incorporated into membranes, or esterified by ACAT in ER and stored in lipid droplets. Excess cholesterol in ER inhibits SREBP processing and downregulates sterol synthesis and import. (B) Inhibition of ACAT1 activity in CD8 T cells increases cholesterol level in plasma membrane and enhances TCR signaling and cytotoxic lymphocyte functions. Genetic deletion of ACAT1 also leads to the upregulation of SREBP transcriptional activity, providing additional potential mechanisms for increased proliferation and function. Cell Metabolism 2016 23, 963-964DOI: (10.1016/j.cmet.2016.05.015) Copyright © 2016 Elsevier Inc. Terms and Conditions