Metabolism of T Lymphocytes in Health and Disease

Gaber, Timo; Chen, Yuling; Krauß, Pierre-Louis; Buttgereit, Frank

doi:10.1016/bs.ircmb.2018.06.002

Cited by 21 publications

(26 citation statements)

References 218 publications

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“…Bulk of NADH and FADH 2 entering ETC reaction in T cells are generated either during tricarboxylic acid (TCA) cycle or from fatty acid oxidation (4). Finally, glutaminolysis involves breakdown of glutamine into glutamate, followed by conversion of glutamate into anaplerotic substrate α-ketoglutarate (α-KG) that fuels cellular proliferation (6)(7)(8). While naïve CD8 + T cells depend predominantly on basal glycolysis and oxidative phosphorylation fueled by fatty acid oxidation to generate ATP for their survival (9)(10)(11)(12), activated T cells upregulate aerobic glycolysis (10,(12)(13)(14) and glutaminolysis (15).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Reprogramming in CD8+ T Cells During Acute Viral Infections

2020

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CD8 + T cells represent one of the most versatile immune cells critical for clearing away viral infections. Due to their important role, CD8 + T cell activation and memory formation during viral infection have been the focus of several studies recently. Although CD8 + T cell activation and memory formation have been associated with metabolic alterations, the molecular understanding behind T cells choosing one type of metabolism over others based on their differentiation stage is still unclear. This review focuses on how the signaling molecules and cellular processes that are characteristic of CD8 + T cell activation and memory formation also play a critical role in selecting specific type of metabolism during viral infections. In addition, we will summarize the epigenetic factors regulating these metabolic alterations.

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Section: Introductionmentioning

confidence: 99%

Metabolic Reprogramming in CD8+ T Cells During Acute Viral Infections

2020

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“…Since ROS synthesis is essential for physiological immune activation of lymphocytes but lead to cellular damage if concentration surpasses (Alfatni et al, 2020), this parameter should be determined in PBMC of diabetic pigs, in order to evaluate whether immune cells are impaired by oxidative cell stress. On the contrary, mitochondrial respiration with increased oxygen consumption is used by immune cells to supplement increased glycolysis, which is the main metabolic pathway fueling effector function upon T cell activation (Gaber, Chen, Krauss, & Buttgereit, 2019). Besides increased oxygen consumption rates, we also found a higher basal glycolytic activity in early diabetic pigs, suggesting that hyperglycaemia induced metabolic adaption to local conditions of immune cells and promoted a more activated status in T cells (Bonacina, Baragetti, Catapano, & Norata, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Besides increased oxygen consumption rates, we also found a higher basal glycolytic activity in early diabetic pigs, suggesting that hyperglycaemia induced metabolic adaption to local conditions of immune cells and promoted a more activated status in T cells (Bonacina, Baragetti, Catapano, & Norata, 2019). A rapid increase in glycolysis is an important determinant in cellular energy production and required for effective cell proliferation, size expansion, and differentiation (Gaber et al, 2019). Hence, it is also possible that PBMC in young diabetic pigs are highly metabolically active to challenge hyperglycaemic conditions.…”

Section: Discussionmentioning

confidence: 99%

Chronic hyperglycaemia drives functional impairment of lymphocytes in diabeticINS^C94Ytransgenic pigs

Giese¹,

Wolf

Hauck

et al. 2020

Preprint

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People with diabetes mellitus have an increased risk for infections, however, there is still a critical gap in precise knowledge about altered immune mechanisms in this disease. Since diabetic INSC94Y transgenic pigs exhibit elevated blood glucose and a stable diabetic phenotype soon after birth, they provide a favourable model to explore functional alterations of immune cells in an early stage of diabetes mellitus in vivo. Hence, we investigated peripheral blood mononuclear cells (PBMC) of these pigs compared to non-transgenic wild-type littermates. We found a 5-fold decreased proliferative response of T cells, disturbed by chronic hyperglycaemia, to polyclonal T cell mitogen phytohaemagglutinin (PHA) and significant increases in mitochondrial oxygen consumption and basal glycolytic activity in PBMC of diabetic pigs. Using LC-MS/MS, we analysed the porcine CD4+ T cell proteome with a total of 2,704 quantified proteins and identified important differences in protein abundances in young diabetic pigs indicating distinct proteomic changes in T cells at initial stage diabetes mellitus.

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“…Indeed, intracellular C1q can directly augment mitochondrial ROS production by cortical neurons in a model of neonatal hypoxic-ischaemic brain injury (Ten et al, 2010) (Figure 3b). Also, cell-autonomous production and intracellular activity of the C1q-TNF hybrid CTRP3 drives OXPHOS-supported protein expression and mitochondrial ROS production within smooth muscle cells (Feng et al, 2016), and gC1qR engagement on mitochondria inhibits the mitochondrial permeability transition pore and protects against oxidative stress-induced death and regulates ATP generation McGee, Douglas, Liang, Hyder, & Baines, 2011) (Figure 3b). A recent elegant study by Marina Botto and colleagues also dissected why C1q, but not C3 deficiency, is associated with SLE.…”

Section: Direct Effects Of Complosome Activity On Mitochondriamentioning

confidence: 99%

Complement's favourite organelle—Mitochondria?

Rahman

Singh

Merle

et al. 2020

British J Pharmacology

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The complement system, well known for its central role in innate immunity, is currently emerging as an unexpected, cell-autonomous, orchestrator of normal cell physiology. Specifically, an intracellularly active complement system-the complosome-controls key pathways of normal cell metabolism during immune cell homeostasis and effector function. So far, we know little about the exact structure and localization of intracellular complement components within and among cells. A common scheme, however, is that they operate in crosstalk with other intracellular immune sensors, such as inflammasomes, and that they impact on the activity of key subcellular compartments. Among cell compartments, mitochondria appear to have built a particularly early and strong relationship with the complosome and extracellularly active complement-not surprising in view of the strong impact of the complosome on metabolism. In this review, we will hence summarize the current knowledge about the close complosome-mitochondria relationship and also discuss key questions surrounding this novel research area.

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Metabolism of T Lymphocytes in Health and Disease

Cited by 21 publications

References 218 publications

Metabolic Reprogramming in CD8+ T Cells During Acute Viral Infections

Metabolic Reprogramming in CD8+ T Cells During Acute Viral Infections

Chronic hyperglycaemia drives functional impairment of lymphocytes in diabeticINS^C94Ytransgenic pigs

Complement's favourite organelle—Mitochondria?

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Metabolism of T Lymphocytes in Health and Disease

Cited by 21 publications

References 218 publications

Metabolic Reprogramming in CD8+ T Cells During Acute Viral Infections

Metabolic Reprogramming in CD8+ T Cells During Acute Viral Infections

Chronic hyperglycaemia drives functional impairment of lymphocytes in diabeticINSC94Ytransgenic pigs

Complement's favourite organelle—Mitochondria?

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Resources

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Chronic hyperglycaemia drives functional impairment of lymphocytes in diabeticINS^C94Ytransgenic pigs