Mechanistic target of rapamycin (mTOR) (mTOR)

The mechanistic target of rapamycin (mTOR) is a conserved serine/threonine kinase (UniProt P42345) that functions as a central rheostat for nutrient sensing and metabolic regulation. In regulatory T cells (Tregs), the mTOR–S6 signaling axis, primarily driven by the mTOR complex 1 (mTORC1), is essential for translating environmental signals into the metabolic programs required for suppressive function (Zeng et al., Nature 2013). Activation of mTORC1 leads to the phosphorylation of p70 ribosomal S6 kinase (S6K1), which in turn phosphorylates ribosomal protein S6 (UniProt P62753), promoting protein translation and cellular growth. While basal mTOR activity is necessary for Treg fitness, hyperactivation of this axis can lead to the loss of the lineage-defining transcription factor Foxp3, causing Tregs to acquire pro-inflammatory effector characteristics (Procaccini et al., Immunity 2010). Pharmacological modulation of this axis, most notably through the use of mTOR inhibitors like sirolimus, is a clinical strategy used to promote immune tolerance in transplantation and autoimmune disorders (Battaglia et al., Diabetes 2006). By fine-tuning the mTOR–S6 axis, researchers aim to stabilize Treg populations and enhance their ability to suppress aberrant immune responses.

Other names

Mammalian target of rapamycinFK506-binding protein 12-rapamycin-associated protein 1FRAPRAFT1mTORC1mTOR-S6 axismTOR-S6K1 pathway

Inhibition of the mTOR kinase complex 1 (mTORC1), which prevents the phosphorylation of p70 ribosomal S6 kinase (S6K1), subsequently inhibiting the phosphorylation of ribosomal protein S6 and modulating regulatory T cell stability and suppressive capacity (Zeng et al., 2013; UniProt P42345).