Regulation and function of mTOR signalling in T cell fate decisions

Regulation and function of mTOR signalling in T cell fate decisions

20 April 2012 | Hongbo Chi
The mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that plays a central role in regulating cell growth and metabolism in eukaryotes. In T cells, mTOR signaling integrates immune signals and metabolic cues to maintain proper T cell function and activation. Under steady-state conditions, mTOR is tightly regulated to ensure T cell homeostasis. Antigen recognition by naive CD4⁺ and CD8⁺ T cells activates mTOR, which programs these cells into distinct functional lineages. This review focuses on the signaling mechanisms of mTOR in T cell homeostasis and function, and discusses the therapeutic implications of targeting mTOR in T cells. mTOR exists in two multiprotein complexes, mTORC1 and mTORC2. mTORC1 is sensitive to rapamycin and is involved in promoting translation initiation and protein synthesis, while mTORC2 is important for the full activation of AKT. mTOR signaling is regulated by various signals, including immune activation signals, growth factors, immunomodulatory factors, and nutrients. The TSC1-TSC2 complex integrates signals from the PI3K-AKT and AMPK pathways to regulate mTOR activity. mTORC1 is activated by amino acids through the RAG family of small GTPases and by RHEB, which is regulated by the TSC complex. mTORC2 is involved in the activation of AKT and the phosphorylation of various protein kinases, including PKCθ and SGK1. mTOR signaling is crucial for T cell homeostasis and differentiation. It regulates cell cycle progression, metabolic programming, and migratory activity. mTORC1 is involved in promoting the differentiation of T helper 1 (TH1), T helper 2 (TH2), and T helper 17 (TH17) cells, while mTORC2 is required for TH2 cell differentiation. mTOR signaling also plays a role in the differentiation of memory CD8⁺ T cells and regulatory T cells (TReg). The inhibition of mTOR with rapamycin can induce the differentiation of anergic and regulatory T cells, as well as memory CD8⁺ T cells. mTOR signaling is also involved in the regulation of T cell metabolism and trafficking. It links metabolic cues to immune signaling and transcriptional networks, ensuring that the metabolic program and migratory activity of a T cell match its cell fate decision. mTORC1 and mTORC2 have distinct effects on immune receptor signaling, with mTORC1 promoting the differentiation of TH1, TH17, and memory CD8⁺ T cells, while mTORC2 is required for TH2 cell differentiation. The regulation of mTOR signaling is crucial for T cell homeostasis and function, and targeting mTOR has therapeutic implications in immune-related diseases.The mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that plays a central role in regulating cell growth and metabolism in eukaryotes. In T cells, mTOR signaling integrates immune signals and metabolic cues to maintain proper T cell function and activation. Under steady-state conditions, mTOR is tightly regulated to ensure T cell homeostasis. Antigen recognition by naive CD4⁺ and CD8⁺ T cells activates mTOR, which programs these cells into distinct functional lineages. This review focuses on the signaling mechanisms of mTOR in T cell homeostasis and function, and discusses the therapeutic implications of targeting mTOR in T cells. mTOR exists in two multiprotein complexes, mTORC1 and mTORC2. mTORC1 is sensitive to rapamycin and is involved in promoting translation initiation and protein synthesis, while mTORC2 is important for the full activation of AKT. mTOR signaling is regulated by various signals, including immune activation signals, growth factors, immunomodulatory factors, and nutrients. The TSC1-TSC2 complex integrates signals from the PI3K-AKT and AMPK pathways to regulate mTOR activity. mTORC1 is activated by amino acids through the RAG family of small GTPases and by RHEB, which is regulated by the TSC complex. mTORC2 is involved in the activation of AKT and the phosphorylation of various protein kinases, including PKCθ and SGK1. mTOR signaling is crucial for T cell homeostasis and differentiation. It regulates cell cycle progression, metabolic programming, and migratory activity. mTORC1 is involved in promoting the differentiation of T helper 1 (TH1), T helper 2 (TH2), and T helper 17 (TH17) cells, while mTORC2 is required for TH2 cell differentiation. mTOR signaling also plays a role in the differentiation of memory CD8⁺ T cells and regulatory T cells (TReg). The inhibition of mTOR with rapamycin can induce the differentiation of anergic and regulatory T cells, as well as memory CD8⁺ T cells. mTOR signaling is also involved in the regulation of T cell metabolism and trafficking. It links metabolic cues to immune signaling and transcriptional networks, ensuring that the metabolic program and migratory activity of a T cell match its cell fate decision. mTORC1 and mTORC2 have distinct effects on immune receptor signaling, with mTORC1 promoting the differentiation of TH1, TH17, and memory CD8⁺ T cells, while mTORC2 is required for TH2 cell differentiation. The regulation of mTOR signaling is crucial for T cell homeostasis and function, and targeting mTOR has therapeutic implications in immune-related diseases.
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