The Mammalian Target of Rapamycin: Linking T Cell Differentiation, Function, and Metabolism

Abstract

Summary In the two signal model of T cell activation, the outcome of antigen recognition is determined by the integration of multiple cues in the immune microenvironment. mTOR is an evolutionarily conserved PI3-kinase family member that plays a central role in integrating environmental cues in the form of amino acids, energy, and growth factors. Recently, an increasingly important role for mTOR in directing T cell activation and differentiation has become apparent. Here we review recent findings demonstrating the ability of mTOR to interpret signals in the immune microenvironment and program the generation of CD4+ effector versus regulatory T cells, the generation of CD8+ effector versus memory cells, T cell trafficking, and T cell activation versus anergy. The key theme to emerge from these studies is that the central role of mTOR provides a direct link between T cell metabolism and function.

The impaired intestinal mucosal immune system by valine deficiency for young grass carp (Ctenopharyngodon idella) is associated with decreasing immune status and regulating tight junction proteins transcript abundance in the intestine

“…Correlation analysis indicated that the expression of IL-8 in the PI and MI, as well as that of TNF-a in the PI and DI were negatively correlated with IkBa ( Table 5), suggesting that valine deficiency may promote NF-kB P65 translocation to the nucleus to enhance TNF-a and IL-8 gene expression by the down-regulation of IkBa expression in fish. Additional, Powell and Delgoffe [70] indicated that mTOR signaling pathway has been found to be involved in regulating the expression of cytokines in terrestrial animal. It was reported that inhibited mTOR expression increased TNF-a production and decreased the release of IL-10 in human [14].…”

Dietary phenylalanine-improved intestinal barrier health in young grass carp (Ctenopharyngodon idella) is associated with increased immune status and regulated gene expression of cytokines, tight junction proteins, antioxidant enzymes and related signalling molecules

“…In mammals, production of cytokine can be modulated by the intracellular signalling molecules [56]. Signaling molecules NF-kB [57] and TOR [58] are critical factors mediating expression of cytokines in animals. Thus, we next addressed the effects of Phe on the expression of NF-kB P65, IkBa and TOR gene in young grass carp.…”

LAT1 Is a Critical Transporter of Essential Amino Acids for Immune Reactions in Activated Human T Cells

“…If T cells cannot ensure that cytosolic amino acid resources are more than sufficient, they will activate an amino acid starvation response, which will downshift an intracellular immune response. However, although mTOR and GCN2 seem to have some functions in T cells (15)(16)(17)(18)(19), little is known about the molecular mechanisms leading to downregulation of immune response induced by amino acid deprivation in T cells.…”