mTORC1 couples immune signals and metabolic programming to establish Treg-cell function

Nature, Journal Year: 2013, Volume and Issue: 499(7459), P. 485 - 490

Published: June 28, 2013

Language: Английский

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The Balance of Th17 versus Treg Cells in Autoimmunity

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(3), P. 730 - 730

Published: March 3, 2018

T helper type 17 (Th17) cells and pTreg cells, which share a common precursor cell (the naïve CD4 cell), require tumor growth factor (TGF)-β signal for initial differentiation. However, terminally differentiated fulfill opposite functions: Th17 cause autoimmunity inflammation, whereas Treg inhibit these phenomena maintain immune homeostasis. Thus, unraveling the mechanisms that affect Th17/Treg balance is critical if we are to better understand tolerance. Recent studies have identified many factors influence this balance; range from signaling pathways triggered by receptors, costimulatory cytokines, various metabolic intestinal microbiota. This review article summarizes recent advances in our understanding of its implications with respect autoimmune disease.

Language: Английский

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Lactate metabolism in human health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 1, 2022

Abstract The current understanding of lactate extends from its origins as a byproduct glycolysis to role in tumor metabolism, identified by studies on the Warburg effect. shuttle hypothesis suggests that plays an important bridging signaling molecule coordinates among different cells, organs and tissues. Lactylation is posttranslational modification initially reported Professor Yingming Zhao’s research group 2019. Subsequent confirmed lactylation vital component function involved proliferation, neural excitation, inflammation other biological processes. An indispensable substance for various physiological cellular functions, regulatory aspects energy metabolism signal transduction. Therefore, comprehensive review summary presented clarify disease provide reference direction future research. This offers systematic overview homeostasis roles pathological processes, well effects diseases, particularly cancer.

Language: Английский

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mTORC1 signaling and the metabolic control of cell growth

Current Opinion in Cell Biology, Journal Year: 2017, Volume and Issue: 45, P. 72 - 82

Published: April 1, 2017

Language: Английский

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Paths to stemness: building the ultimate antitumour T cell

Nature reviews. Cancer, Journal Year: 2012, Volume and Issue: 12(10), P. 671 - 684

Published: Sept. 21, 2012

Language: Английский

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The TSC-mTOR pathway regulates macrophage polarization

Nature Communications, Journal Year: 2013, Volume and Issue: 4(1)

Published: Nov. 27, 2013

Language: Английский

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Molecular regulation of effector and memory T cell differentiation

Nature Immunology, Journal Year: 2014, Volume and Issue: 15(12), P. 1104 - 1115

Published: Nov. 14, 2014

Language: Английский

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Regulation and metabolic functions of mTORC1 and mTORC2

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(3), P. 1371 - 1426

Published: Feb. 18, 2021

Cells metabolize nutrients for biosynthetic and bioenergetic needs to fuel growth proliferation. The uptake of from the environment their intracellular metabolism is a highly controlled process that involves cross talk between signaling metabolic pathways. Despite constant fluctuations in nutrient availability environmental signals, normal cells restore homeostasis maintain cellular functions prevent disease. A central molecule integrates with mechanistic target rapamycin (mTOR). mTOR protein kinase responds levels signals. forms two complexes, mTORC1, which sensitive rapamycin, mTORC2, not directly inhibited by this drug. Rapamycin has facilitated discovery various mTORC1 metabolism. Genetic models disrupt either or mTORC2 have expanded our knowledge cellular, tissue, as well systemic Nevertheless, regulation particularly metabolism, lagged behind. Since an important cancer, aging, other metabolism-related pathologies, understanding distinct overlapping complexes vital development more effective therapeutic strategies. This review discusses key discoveries recent findings on complexes. We highlight cancer but also discuss examples mTOR-mediated reprogramming occurring stem immune cells, type 2 diabetes/obesity, neurodegenerative disorders, aging.

Language: Английский

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T cell stemness and dysfunction in tumors are triggered by a common mechanism

Science, Journal Year: 2019, Volume and Issue: 363(6434)

Published: March 28, 2019

A paradox of tumor immunology is that tumor-infiltrating lymphocytes are dysfunctional in situ, yet capable stem cell-like behavior including self-renewal, expansion, and multipotency, resulting the eradication large metastatic tumors. We find overabundance potassium microenvironment underlies this dichotomy, triggering suppression T cell effector function while preserving stemness. High levels extracellular constrain programs by limiting nutrient uptake, thereby inducing autophagy reduction histone acetylation at exhaustion loci, which turn produces CD8+ cells with improved vivo persistence, clearance. This mechanistic knowledge advances our understanding dysfunction may lead to novel approaches enable development enhanced strategies for cancer immunotherapy.

Language: Английский

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Metabolic checkpoints in activated T cells

Nature Immunology, Journal Year: 2012, Volume and Issue: 13(10), P. 907 - 915

Published: Sept. 18, 2012

Language: Английский

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