Sterol regulatory element–binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity

Tsc1 promotes the differentiation of memory CD8 + T cells via orchestrating the transcriptional and metabolic programs

“…The metabolic programs are dynamically regulated to match the differentiation and function of T cells (4)(5)(6). For the fate decisions between effector and memory CD8 + T cells, the glycolytic and lipid synthetic metabolism promotes effector T-cell generation (7,11), whereas oxidative phosphorylation and mitochondrial activity facilitate memory development (12,13). From the microarray and bioinformatics analyses, we found that Tsc1 −/− antigen-specific CD8 + T cells exhibit elevated expression of metabolic genes involved in glycolysis, lipid synthesis, and oxidative phosphorylation.…”

“…Naïve and memory T cells use catabolic metabolism via oxidative phosphorylation, especially fatty acid oxidation, to produce ATP for their survival. In contrast, antigen-stimulated T cells switch to anabolism to support their rapid proliferation through up-regulating expression of genes involved in multiple metabolic pathways, including glycolysis, fatty acid and cholesterol biosynthesis, and amino acid transport (7)(8)(9)(10). Emerging studies indicate that distinct metabolic pathways contribute to the fate decisions of effector and memory T cells.…”

The Epigenetic Drug 5-Azacytidine Interferes with Cholesterol and Lipid Metabolism

“…Increased SREBP signaling in bone marrow and peripheral blood cells of patients with MDS has been associated with poor survival prognosis (50). In addition, it was demonstrated that the activation of the SREBP pathway protects cancer cells from lipotoxicity (51) and promotes growth of activated CD8 ϩ T lymphocytes (52), which expand in MDS patients (53). Through the mevalonate pathway, SREBPs also provide key intermediates required for the isoprenylation of small GTPases, such as farnesylation of Ras and geranylgeranylation of Rho, both involved in cancer progression and metastatic dissemination (54).…”

Impact of environmental factors on alloimmunity and transplant fate

“…T cell-specific deletion of the ATP-binding cassette transporter G1 (ABCG1), which promotes cellular cholesterol efflux, enhanced T cell receptor (TCR) signaling (55). SREBP-deficient CD8 + T cells displayed defective proliferation and deficient clonal expansion during viral infection (56). Inhibition of ACAT1, a cholesterol esterification enzyme, led to increased CD8 + T cell cytotoxicity, TCR clustering, and TCR signaling (57).…”