CD8+ T cell metabolism in infection and cancer

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(11), P. 718 - 738

Published: May 12, 2021

Language: Английский

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Metabolism of tissue macrophages in homeostasis and pathology

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 19(3), P. 384 - 408

Published: Dec. 7, 2021

Abstract Cellular metabolism orchestrates the intricate use of tissue fuels for catabolism and anabolism to generate cellular energy structural components. The emerging field immunometabolism highlights importance maintenance activities immune cells. Macrophages are embryo- or adult bone marrow-derived leukocytes that key healthy homeostasis but can also contribute pathologies such as metabolic syndrome, atherosclerosis, fibrosis cancer. Macrophage has largely been studied in vitro. However, different organs contain diverse macrophage populations specialize distinct often tissue-specific functions. This context specificity creates diverging challenges fulfill their homeostatic roles particular microenvironment conditions response pathological conditions. Here, we outline current knowledge on requirements adaptations macrophages located tissues during selected diseases.

Language: Английский

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Global absence and targeting of protective immune states in severe COVID-19

Nature, Journal Year: 2021, Volume and Issue: 591(7848), P. 124 - 130

Published: Jan. 25, 2021

Although infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has pleiotropic and systemic effects in some individuals1-3, many others experience milder symptoms. Here, to gain a more comprehensive understanding of the distinction between mild phenotypes pathology disease 2019 (COVID-19) its origins, we performed whole-blood-preserving single-cell analysis protocol integrate contributions from all major immune cell types blood-including neutrophils, monocytes, platelets, lymphocytes contents serum. Patients COVID-19 exhibit coordinated pattern expression interferon-stimulated genes (ISGs)3 across every population, whereas these ISG-expressing cells are systemically absent patients disease. Paradoxically, individuals produce very high titres anti-SARS-CoV-2 antibodies have lower viral load compared Examination serum shows that uniquely functionally block production associated disease, by activating conserved signalling circuits dampen cellular responses interferons. Overzealous antibody pit system against itself COVID-19, perhaps also other infections. Our findings reveal potential targets for immunotherapies re-engage defence.

Language: Английский

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Spatiotemporal co-dependency between macrophages and exhausted CD8+ T cells in cancer

Cancer Cell, Journal Year: 2022, Volume and Issue: 40(6), P. 624 - 638.e9

Published: May 26, 2022

Language: Английский

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Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(2), P. 179 - 192

Published: Jan. 18, 2021

Language: Английский

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Rewiring the altered tryptophan metabolism as a novel therapeutic strategy in inflammatory bowel diseases

Gut, Journal Year: 2022, Volume and Issue: 72(7), P. 1296 - 1307

Published: Oct. 21, 2022

The extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp end-products are essential intestinal homeostasis. Here, we investigated role metabolites from kynurenine pathway.Targeted quantitative metabolomics was performed in two large human IBD cohorts (1069 patients with IBD). Dextran sodium sulphate-induced colitis experiments mice were used evaluate effects identified metabolites. In vitro, ex vivo and decipher mechanisms involved. Effects on energy evaluated by different methods including Single Cell mEtabolism profiling Translation inHibition.In humans, inflammation severity negatively correlates amount xanthurenic (XANA) kynurenic (KYNA) acids. Supplementation XANA KYNA decreases through epithelial cells T cells, involving Aryl hydrocarbon Receptor (AhR) activation rewiring cellular metabolism. Furthermore, direct modulation endogenous metabolism, using recombinant enzyme aminoadipate aminotransferase (AADAT), responsible for generation KYNA, protective rodent models.Our study a new mechanism linking IBD. Bringing back has AhR CD4+ cells. This paves way therapeutic strategies aiming at pharmacologically correcting its manipulating metabolic pathway AADAT.

Language: Английский

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Discovering dominant tumor immune archetypes in a pan-cancer census

Cell, Journal Year: 2021, Volume and Issue: 185(1), P. 184 - 203.e19

Published: Dec. 27, 2021

Language: Английский

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Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19

Nature, Journal Year: 2022, Volume and Issue: 609(7928), P. 801 - 807

Published: July 28, 2022

Language: Английский

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To metabolomics and beyond: a technological portfolio to investigate cancer metabolism

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 22, 2023

Abstract Tumour cells have exquisite flexibility in reprogramming their metabolism order to support tumour initiation, progression, metastasis and resistance therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosynthetic redox status sustain increased energetic demand cells. Over last decades, cancer field has seen an explosion new biochemical technologies giving more tools than ever before navigate this complexity. Within cell or tissue, metabolites constitute direct signature molecular phenotype thus profiling concrete clinical applications oncology. Metabolomics fluxomics, are key technological approaches that mainly revolutionized enabling researchers both qualitative mechanistic model cancer. Furthermore, upgrade from bulk single-cell analysis provided unprecedented opportunity investigate biology at cellular resolution allowing depth quantitative complex heterogenous diseases. More recently, advent functional genomic screening allowed identification pathways, processes, biomarkers novel therapeutic targets concert with other allow patient stratification treatment regimens. This review is intended be guide for metabolism, highlighting current emerging technologies, emphasizing advantages, disadvantages potential leading development innovative anti-cancer

Language: Английский

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Carbon source availability drives nutrient utilization in CD8+ T cells

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(9), P. 1298 - 1311.e6

Published: Aug. 17, 2022

How environmental nutrient availability impacts T cell metabolism and function remains poorly understood. Here, we report that the presence of physiologic carbon sources (PCSs) in culture medium broadly glucose utilization by CD8+ cells, independent transcriptional changes metabolic reprogramming. The PCSs reduced contribution to TCA cycle increased effector with lactate directly fueling cycle. In fact, cells responding Listeria infection preferentially consumed over as a substrate vitro, enhancing bioenergetic biosynthetic capacity. Inhibiting lactate-dependent silencing dehydrogenase A (Ldha) impaired both homeostasis proliferative expansion vivo. Together, our data indicate source shapes identifies fuel for cells.

Language: Английский

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