Regulation and function of mTOR signalling in T cell fate decision

By Hongbo Chi. Nature reviews. Immunology, 2012

932 citations recorded by the source corpus.

The evolutionarily conserved kinase mTOR (mammalian target of rapamycin) couples cell growth and metabolism to environmental inputs in eukaryotes. T cells depend on mTOR signalling to integrate immune signals and metabolic cues for their proper maintenance and activation. Under steady-state conditions, mTOR is actively controlled by multiple inhibitory mechanisms, and this enforces normal T cell homeostasis. Antigen recognition by naive CD4+ and CD8+ T cells triggers mTOR activation, which in turn programmes the differentiation of these cells into functionally distinct lineages. This Review focuses on the signalling mechanisms of mTOR in T cell homeostatic and functional fates, and discusses the therapeutic implications of targeting mTOR in T cells.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ded855171c1c774298917c6888787ab72d3334ca

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Citations in the corpus

The Balance of Th17 versus Treg Cells in Autoimmunity (2018, background): “When naïve T cells are activated, mTOR is activated and acts as a critical regulator that modulates T cell differentiation and function [71].”
Metabolic Pathways In Immune Cell Activation And Quiescence (2013, background): “More specifically, metabolic pathways can influence the development of various T helper subsets, and this has also been the subject of several reviews (Chi, 2012; Gerriets and Rathmell, 2012; Zemirli and Arnoult, 2012).”
Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease (2023, background): “198 These signals have been found to involve cytokines, co-stimulatory molecules, and antigenic signals as well as environmental cues derived nutrients, growth, and immunoregulatory factors.”
Metabolic Regulation of T Lymphocytes (2013, background): “Downstream of Akt, activation of mTORC1 also promotes posttranslational events to stimulate aerobic glycolysis and coordinate pathways to support cell growth (64).”
Glucose Metabolism Regulates T Cell Activation, Differentiation, and Functions (2014, background): “This intimate interrelationship between T cell activation and metabolism led to the concept that changes in T cell metabolism are not simply a consequence of antigen-induced activation, but rather a parameter that determines T cell proliferation and fate decisions (5, 24).”
Targeting PI3K/Akt/mTOR Signaling in Cancer (2014, background): “Metabolic and immune-related adverse events are clearly ontarget effects of mTOR inhibition, while cutaneous and mucosal effects may have a less direct association with mTOR inhibition, although inhibition of mTOR-mediated growth and tissue repair and/or immune dysregulation have been proposed to be”
Causes, consequences, and reversal of immune system aging. (2013, positive): “For example, inhibition of mTOR, a PI3K pathway intermediate, with rapamycin has been shown to stimulate CD8 + T cell responses in preclinical studies (110).”
mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity (2014, background): “mTOR acts as a sensor of the metabolic environment (21) and functions as amaster regulator of glucose metabolism in activated lymphocytes (22).”
The PI3K pathway in human disease (2017, neutral): “The roles of mTORC1 and mTORC2 in the metabolic programming and differentiation of effector lymphocytes is another topic that has been thoroughly reviewed (Chi, 2012; Jellusova and Rickert, Cell 170 , August 10, 2017 613 2016; Waickman and Powell, 2012).”