mTOR in T_reg cells

The metabolic regulator mTOR senses nutrient availability and influences cell functionality. In Nature, Chi and colleagues show that mTORC1 directs regulatory T (T_reg) cell function in vivo. Targeted deletion of raptor, a component of mTORC1, leads to loss of ICOS and CTLA-4 expression, although CD25 and Foxp3 expression is not altered. Mice whose T_reg cells lack raptor develop a 'scurfy-like' autoimmune disease, consistent with a loss of effective suppressor cells. Conversely, targeted loss of rictor, which forms mTORC2 complexes, does not alter T_reg cell function. Interestingly, loss of mTORC1 also decreases cholesterol biosynthesis and lipid metabolism. Pharmacologic inhibition of cholesterol biosynthesis in wild-type T_reg cells likewise decreases T_reg cell suppressive ability, whereas addition of mevalonate, a key intermediate in this pathway, restores suppressive activity. Thus, mTORC1 regulates T_reg cell function by influencing cholesterol biosynthesis and inhibitory costimulation molecules.

Nature 499, 485–490 (2013)