mTOR, metabolism, and the regulation of T-cell differentiation and function

Abstract

Upon antigen recognition, naive T cells undergo rapid expansion and activation. The energy requirements for this expansion are formidable, and T-cell activation is accompanied by dramatic changes in cellular metabolism. Furthermore, the outcome of antigen engagement is guided by multiple cues derived from the immune microenvironment. Mammalian target of rapamycin (mTOR) is emerging as a central integrator of these signals playing a critical role in driving T-cell differentiation and function. Indeed, multiple metabolic programs are controlled by mTOR signaling. In this review, we discuss the role of mTOR in regulating metabolism and how these pathways intersect with the ability of mTOR to integrate cues that guide the outcome of T-cell receptor engagement.

Fig. 1. mTOR integrates environmental signals to coordinate the metabolic and immunologic programs

mTOR is emerging as a critical integrator of environmental cues guiding T-cell differentiation and function. mTOR also plays a critical role in regulating cellular metabolic programs. In as much as the upregulation of specific metabolic programs is critical for the activation of T cells, mTOR signaling serves to coordinate T-cell differentiation and metabolism.

Fig. 2. mTOR regulates expression of metabolic genes via transcriptional programs

Following activation by intrinsic and extrinsic cues, mTOR regulates transcription factors involved in coordinating glycolysis (HIF-1α, Myc), fatty acid oxidation (PPAR α, PPARγ), as well as fatty acid synthesis (SREBP). These same factors have been implicated in regulating T-cell differentiation and function upon antigen recognition.