Fig. 2

Lipid metabolism enhances treg-mediated immunosuppression. Lipid metabolism is conducive to the expression of PD-1, CTLA-4, ICOS, and FOXP3 in Tregs, enhancing immunosuppressive ability. Free fatty acids uptake enhances FAO through activating the PPAR pathway. Inhibition of PI3K-AKT-mTORC1 pathway-mediated glycolysis is conducive to the enhancement of FAO. PTEN, AMPK, PP2A, HIF2α, and FOXP3 are inhibitory molecules of the PI3K-AKT-mTORC1 pathway, which attenuate glycolysis. Oleic acids, increased reactive oxygen species levels, and PD1/CTLA-4 signal transduction are beneficial to the expression of FOXP3, inhibit glycolysis, and promote FAO. FAS is essential for the expression of immunosuppressive molecules. Here, a large amount of acetyl-coa produced by glycolysis can be used as a substrate for the synthesis of fatty acids and cholesterol, where mTORC1 has been reported to upregulate expression of CTLA-4, ICOS by activating the mevalonate pathway. Activation of the mevalonate pathway is also associated with enhanced PD-1 expression