Fatty acid remodeling in cellular glycerophospholipids following the activation of human T cells

Robichaud, Philippe Pierre; Boulay, Katherine; Munganyiki, Jean Eric; Surette, Marc E.

doi:10.1194/jlr.m037044

Cited by 31 publications

(41 citation statements)

References 76 publications

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“…Lipid macro-molecules are a major physical constitute of cells (2, 4). Therefore, it is logical to speculate that limiting these “building block” molecules may have negative effects on survival during cell division.…”

Section: Resultsmentioning

confidence: 99%

Regulator of Fatty Acid Metabolism, Acetyl Coenzyme A Carboxylase 1, Controls T Cell Immunity

Lee

Walsh

Hoehn

et al. 2014

The Journal of Immunology

163

125

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Fatty acids (FA) are essential constituents of cell membranes, signaling molecules, and bioenergetic substrates. As CD8+ T cells undergo both functional and metabolic changes during activation and differentiation, dynamic changes in FA metabolism also occur. However, the contributions of de novo lipogenesis to acquisition and maintenance of CD8+ T cell function are unclear. Here, we demonstrate the role of FA synthesis in CD8+ T cell immunity. T cell-specific deletion of ACC1 (ACC1ΔT), an enzyme that catalyzes conversion of acetyl CoA to malonyl CoA, a carbon donor for long chain FA synthesis, resulted in impaired peripheral persistence and homeostatic proliferation of CD8+ T cells in naïve mice. Loss of ACC1 did not compromise effector CD8+ T cell differentiation upon listeria infection, but did result in a severe defect in Ag-specific CD8+ T cell accumulation due to increased death of proliferating cells. Furthermore, in vitro mitogenic stimulation demonstrated that defective ACC1ΔT CD8+ T cell blast and survival could be rescued by provision of exogenous FA. These results suggest an essential role for ACC1-mediated de novo lipogenesis as a regulator of CD8+ T cell expansion, and may provide insights for therapeutic targets for interventions in autoimmune diseases, cancer, and chronic infections.

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Section: Resultsmentioning

confidence: 99%

Regulator of Fatty Acid Metabolism, Acetyl Coenzyme A Carboxylase 1, Controls T Cell Immunity

Lee

Walsh

Hoehn

et al. 2014

The Journal of Immunology

163

125

View full text Add to dashboard Cite

show abstract

“…AA undergoes a pattern of incorporation into and remodeling between glycerophospholipid classes that appears to be specific for AA compared with other FAs (20,23,53,54). This unique remodeling pattern is believed to have evolved partly because AA is the precursor of very potent bioactive metabolites, and cells have developed mechanisms to tightly control its cellular distribution and bioavailability.…”

Section: Discussionmentioning

confidence: 99%

“…AA undergoes a specific pattern of incorporation into PLs where initial acylation is primarily in PC and PI resulting from reactions catalyzed by ACSs and lyso-PLATs. Once AA is incorporated into PC species, it is then transferred primarily into 1-radyl PE species by a CoA-IT-catalyzed reaction (19)(20)(21)(22)(23)(24). Upon appropriate cell stimulation, AA can be hydrolyzed from PL by PLA 2 and can be converted by LOXs and COXs into many different bioactive lipid mediators, called eicosanoids, which include HETEs, leukotrienes, prostaglandins, and lipoxins (24)(25)(26)(27).…”

Section: Preparation and Stimulation Of Human Neutrophilsmentioning

confidence: 99%

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On the cellular metabolism of the click chemistry probe 19-alkyne arachidonic acid

Robichaud

Poirier

Boudreau

et al. 2016

Journal of Lipid Research

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“…Firstly, it was reported that T cells switch to fatty acid synthesis from fatty acid oxidation upon activation and proliferation [13]. Secondly, Miguel and colleagues also found that T cell proliferation ability is closely correlated with the membrane lipid composition [14].…”

Section: Major Metabolic Pathways Exploited By Immune Cellsmentioning

confidence: 95%

Metabolic Reprogramming in Resting and Activated Immune Cells

Sun

2017

Mol Biol (Los Angel)

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pyruvate with the production of two molecules of ATP. The pyruvate end product of glycolysis can be used in either anaerobic respiration if no oxygen is available or in aerobic respiration via the TCA cycle which yields much more usable energy for the cell. The TCA cycleThe generated pyruvate from glycolysis has two fates. One is to import into the mitochondria and to be converted to acetyl-CoA, entering the TCA cycle to produce NADPH and FADH 2, which can be used to generate ATP in mitochondria.The alternative fate of pyruvate is to be converted to lactate in the cytosol that is an important strategy to regenerate NAD + under hypoxic conditions. The generated NAD + can be used in the process of generating pyruvate from glucose. Oxidative phosphorylation's in mitochondriaThis is a process occuring in mitochondria that NADH and FADH 2 generated from glycolysis and TCA cycles are passed along electron transport chain to oxygen and generate usable energy ATP. Fatty acid metabolismFatty acid metabolism includes two parts: one is catabolic process by which fatty acid is broken down by in mitochondria to generate Acetyl-CoA, which enters TCA cycle and NADH/FADH 2, which are used in oxidative phosphorylation to produce ATP. The other process is anabolic which is opposite to fatty acid oxidation, which is to creat fatty acid using Acetyl-CoA through actions of fatty acid synthase. This process is carried out during cytoplasm. Metabolic Pathways T cell Activation and Proliferation Before T cells encounter any antigens and/or danger signalsKeywords: Glutaminolysis; Metabolic programming; Bio-precursors IntroductionIn steady stage, the cells in immune system are relatively quiescent with minimal activities and survival needs but they possess the ability to quickly respond to pathogens or environmental challenges and constantly orchestrate their effector functions [1]. Once pathogens are detected in the body, the cells will switch to an activated stage and become to fight with possible inflammation, infection, and/or any attacks from environment. The shaping from a quiescent stage to an activated stage requires energy and bio-precursor. Recent studies indicate that metabolism and immune cell functions are closely linked [2]. The change in metabolism not only passively supports the activation status, but also crucially influences the differentiation of immune cells. To understand how these fundamental processes influence each other may provide novel treatments for inflammatory and autoimmune diseases. Cells of the immune systemDefense against invading infectious pathogens and noninfectious foreign substances is mediated by innate immunity and adaptive immunity. Innate immune responses are early reactions of immune system and carried out by innate immune cells including macrophages, neutrophils, and natural killer cells. They provide the first defense barrier and response of protection while adaptive immune responses offer more specific actions to the pathogens. There are two types of adaptive immune responses: antibody-based...

show abstract

Fatty acid remodeling in cellular glycerophospholipids following the activation of human T cells

Cited by 31 publications

References 76 publications

Regulator of Fatty Acid Metabolism, Acetyl Coenzyme A Carboxylase 1, Controls T Cell Immunity

Regulator of Fatty Acid Metabolism, Acetyl Coenzyme A Carboxylase 1, Controls T Cell Immunity

On the cellular metabolism of the click chemistry probe 19-alkyne arachidonic acid

Metabolic Reprogramming in Resting and Activated Immune Cells

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