Immunometabolism最新文献

{"title":"Regulatory T cells and bioenergetics of peripheral blood mononuclear cells linked to pediatric obesity","authors":"Shannon Rose, Reid D. Landes, Kanan K. Vyas, Leanna M. Delhey, Sarah Blossom","doi":"10.1097/in9.0000000000000040","DOIUrl":"https://doi.org/10.1097/in9.0000000000000040","url":null,"abstract":"\u0000 \u0000 Obesity-associated inflammation drives the development of insulin resistance and type 2 diabetes. We sought to identify associations of circulating regulatory T cells (Treg) with the degree of obesity (eg, body mass index Z-score [BMIz]), insulin resistance (homeostatic model of insulin resistance [HOMA-IR]), and glycemic control (HbA1c) in children and adolescents. We further sought to examine associations among bioenergetics of peripheral blood mononuclear cells (PBMCs) and CD4 T cells and BMIz, HOMA-IR, and HbA1c.\u0000 \u0000 \u0000 \u0000 A total of 65 children and adolescents between the ages 5 and 17 years were studied. HbA1c and fasting levels of plasma glucose and insulin were measured. We quantified circulating Tregs (CD3+CD4+CD25+CD127-FoxP3+) by flow cytometry, and measured mitochondrial respiration (oxygen consumption rate [OCR]) and glycolysis (extracellular acidification rate [ECAR]) in PBMCs and isolated CD4 T cells by Seahorse extracellular flux analysis.\u0000 \u0000 \u0000 \u0000 Tregs (% CD4) are negatively associated with BMIz but positively associated with HOMA-IR. In PBMCs, OCR/ECAR (a ratio of mitochondrial respiration to glycolysis) is positively associated with BMIz but negatively associated with HbA1c.\u0000 \u0000 \u0000 \u0000 In children, Tregs decrease as body mass index increases; however, the metabolic stress and inflammation associated with insulin resistance may induce a compensatory increase in Tregs. The degree of obesity is also associated with a shift away from glycolysis in PBMCs but as HbA1c declines, metabolism shifts back toward glycolysis. Comprehensive metabolic assessment of the immune system is needed to better understand the implications immune cell metabolic alterations in the progression from a healthy insulin-sensitive state toward glucose intolerance in children.\u0000 \u0000 \u0000 \u0000 This observational study was registered at the ClinicalTrials.gov (NCT03960333, https://clinicaltrials.gov/study/NCT03960333?term=NCT03960333&rank=1).\u0000","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"42 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140796358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Nuclear Receptors for T_H17-Mediated Inflammation: REV-ERBerations of Circadian Rhythm and Metabolism.","authors":"Sarah A Mosure,&nbsp;Adrianna N Wilson,&nbsp;Laura A Solt","doi":"10.20900/immunometab20220006","DOIUrl":"https://doi.org/10.20900/immunometab20220006","url":null,"abstract":"<p><p>Since their discovery, a significant amount of progress has been made understanding T helper 17 (T_H17) cells' roles in immune homeostasis and disease. Outside of classical cytokine signaling, environmental and cellular intrinsic factors, including metabolism, have proven to be critical for non-pathogenic vs pathogenic T_H17 cell development, clearance of infections, and disease. The nuclear receptor RORγt has been identified as a key regulator of T_H17-mediated inflammation. Nuclear receptors regulate a variety of physiological processes, ranging from reproduction to the circadian rhythm, immunity to metabolism. Outside of RORγt, the roles of other nuclear receptors in T_H17-mediated immunity are not as well established. In this mini-review we describe recent studies that revealed a role for a different member of the nuclear receptor superfamily, REV-ERBα, in the regulation of T_H17 cells and autoimmunity. We highlight similarities and differences between reports, potential roles beyond T_H17-mediated cytokine regulation, unresolved questions in the field, as well as the translational potential of targeting REV-ERBα.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9038092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10415187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Compass to Guide Insights into T_H17 Cellular Metabolism and Autoimmunity.","authors":"Adrianna N Wilson,&nbsp;Sarah A Mosure,&nbsp;Laura A Solt","doi":"10.20900/immunometab20220001","DOIUrl":"https://doi.org/10.20900/immunometab20220001","url":null,"abstract":"<p><p>T cells rapidly convert their cellular metabolic requirements upon activation, switching to a highly glycolytic program to satisfy their increasingly complex energy needs. Fundamental metabolic differences have been established for the development of Foxp3⁺ T regulatory (Treg) cells versus T_H17 cells, alterations of which can drive disease. T_H17 cell dysregulation is a driver of autoimmunity and chronic inflammation, contributing to pathogenesis in diseases such as multiple sclerosis. A recent paper published in <i>Cell</i> by Wagner, et al. combined scRNA-seq and metabolic mapping data to interrogate potential metabolic modulators of T_H17 cell pathogenicity. This Compass to T_H17 cell metabolism highlights the polyamine pathway as a critical regulator of T_H17/Treg cell function, signifying its potential as a therapeutic target.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8654074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10781706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid Metabolism as a New Target for Rejuvenation?-Comments on Restoring Metabolism of Myeloid Cells Reverses Cognitive Decline in Ageing. Nature. 2021 Feb;590(7844):122-128.","authors":"Marlen Knobloch,&nbsp;Rosa C Paolicelli","doi":"10.20900/immunometab20210034","DOIUrl":"https://doi.org/10.20900/immunometab20210034","url":null,"abstract":"<p><p>Research led by Katrin Andreasson suggests that fixing age-induced metabolic defects in myeloid cells would suffice to reverse cognitive impairment and to restore synaptic plasticity to the level of young subjects, at least in mice. This opens up the possibility to develop rejuvenating strategies by targeting immune dysfunction.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"3 4","pages":"e210034"},"PeriodicalIF":0.0,"publicationDate":"2021-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39871698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Altered Cellular Metabolism Underpin the Normal Changes to the Maternal Immune System during Pregnancy?","authors":"Benjamin J Jenkins,&nbsp;April Rees,&nbsp;Nicholas Jones,&nbsp;Catherine A Thornton","doi":"10.20900/immunometab20210031","DOIUrl":"https://doi.org/10.20900/immunometab20210031","url":null,"abstract":"<p><p>Pregnancy is characterised by metabolic changes that occur to support the growth and development of the fetus over the course of gestation. These metabolic changes can be classified into two distinct phases: an initial anabolic phase to prepare an adequate store of substrates and energy which are then broken down and used during a catabolic phase to meet the energetic demands of the mother, placenta and fetus. Dynamic readjustment of immune homeostasis is also a feature of pregnancy and is likely linked to the changes in energy substrate utilisation at this time. As cellular metabolism is increasingly recognised as a key determinant of immune cell phenotype and function, we consider how changes in maternal metabolism might contribute to T cell plasticity during pregnancy.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"3 4","pages":"e210031"},"PeriodicalIF":0.0,"publicationDate":"2021-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39673889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-10-Mediated Refueling of Exhausted T Cell Mitochondria Boosts Anti-Tumour Immunity.","authors":"Dylan Ryan,&nbsp;Christian Frezza","doi":"10.20900/immunometab20210030","DOIUrl":"https://doi.org/10.20900/immunometab20210030","url":null,"abstract":"<p><p>Immunotherapy has underscored a revolution in cancer treatment. Yet, many patients fail to respond due to T cell exhaustion. Here, an intervention that restores mitochondrial function reversed the exhausted T cell phenotype to promote cytotoxicity and durable anti-tumour responses in vivo.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"3 4","pages":"e210030"},"PeriodicalIF":0.0,"publicationDate":"2021-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39496025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interplay between γδT-Cell Metabolism and Tumour Microenvironment Offers Opportunities for Therapeutic Intervention.","authors":"Marta Barisa, Daniel Fowler, Jonathan Fisher","doi":"10.20900/immunometab20210026","DOIUrl":"10.20900/immunometab20210026","url":null,"abstract":"<p><p>Solid tumour targeting using adoptive cell therapy has failed to reproduce the spectacular clinical successes seen with chimeric antigen receptor T cell therapies and B cell malignancies. Low in glucose, oxygen, pH and populated with suppressive cells, the solid tumour microenvironment (TME) remains a formidable obstacle to successful immune targeting. The use of atypical, tissue-tropic lymphocytes, such as γδT cells, may offer enhanced tumour trafficking over canonical αβT cells. Nonetheless, γδT cells too interact with the TME. The consequences of this interaction are poorly understood and of high translational relevance. Lopes and colleagues show that, in a murine context, low glucose environments preferentially retained pro-tumorigenic IL-17-producing γδT cells. Anti-tumorigenic IFN-γ-producing γδT cells, meanwhile, required high ambient glucose to survive and exert effector function. Unexpectedly, this metabolic imprinting was evident in the murine thymus, suggesting that the ontological separation of these functional subsets occurs early in their development. Elucidation of this relationship between TME glucose levels and γδT cell functionality in a human context is likely to carry significant implications for the development of γδT cell-based oncoimmunotherapeutics.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"3 3","pages":"210026"},"PeriodicalIF":0.0,"publicationDate":"2021-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39313457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"oxLDL-Induced Trained Immunity Is Dependent on Mitochondrial Metabolic Reprogramming.","authors":"Laszlo A Groh,&nbsp;Anaisa V Ferreira,&nbsp;Leonie Helder,&nbsp;Charlotte D C C van der Heijden,&nbsp;Boris Novakovic,&nbsp;Els van de Westerlo,&nbsp;Vasiliki Matzaraki,&nbsp;Simone J C F M Moorlag,&nbsp;L Charlotte de Bree,&nbsp;Valerie A C M Koeken,&nbsp;Vera P Mourits,&nbsp;Samuel T Keating,&nbsp;Jelmer H van Puffelen,&nbsp;Alexander Hoischen,&nbsp;Leo A B Joosten,&nbsp;Mihai G Netea,&nbsp;Werner J H Koopman,&nbsp;Niels P Riksen","doi":"10.20900/immunometab20210025","DOIUrl":"https://doi.org/10.20900/immunometab20210025","url":null,"abstract":"<p><p>Following brief exposure to endogenous atherogenic particles, such as oxidized low-density lipoprotein (oxLDL), monocytes/macrophages can adopt a long-term pro-inflammatory phenotype, which is called trained immunity. This mechanism might contribute to the chronic low-grade inflammation that characterizes atherosclerosis. In this study, we aim to elucidate immunometabolic pathways that drive oxLDL-induced trained immunity. Primary isolated human monocytes were exposed to oxLDL for 24 h, and after five days stimulated with LPS to measure the cytokine production capacity. RNA-sequencing revealed broad increases in genes enriched in mitochondrial pathways after 24 h of oxLDL exposure. Further omics profiling of oxLDL-trained macrophages via intracellular metabolomics showed an enrichment for tricarboxylic acid (TCA) cycle metabolites. Single cell analysis revealed that oxLDL-trained macrophages contain larger mitochondria, potentially likely linked to increased oxidative phosphorylation (OXPHOS) activity. Co-incubation with pharmacological blockers of OXPHOS inhibited oxLDL-induced trained immunity. The relevance of OXPHOS was confirmed in a cohort of 243 healthy subjects showing that genetic variation in genes coding for enzymes relevant to OXPHOS correlated with the capacity of monocytes to be trained with oxLDL. Interestingly, OXPHOS appears to play an important role in the increased cytokine hyperresponsiveness by oxLDL-trained macrophages. The TCA-cycle can also be fuelled by glutamine and free fatty acids, and pharmacological blockade of these pathways could prevent oxLDL-induced trained immunity. This study demonstrates that the mitochondria of oxLDL-trained macrophages undergo changes to their function and form with OXPHOS being an important mechanism for trained immunity, which could unveil novel pharmacological targets to prevent atherogenesis.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"3 3","pages":"e210025"},"PeriodicalIF":0.0,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39188594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular Metabolism as Driver of Atherosclerosis: Linking Endothelial Metabolism to Inflammation.","authors":"Kim E Dzobo,&nbsp;Katie M L Hanford,&nbsp;Jeffrey Kroon","doi":"10.20900/immunometab20210020","DOIUrl":"https://doi.org/10.20900/immunometab20210020","url":null,"abstract":"<p><p>The endothelium is a crucial regulator of vascular homeostasis by controlling barrier integrity as well acting as an important signal transducer, thereby illustrating that endothelial cells are not inert cells. In the context of atherosclerosis, this barrier function is impaired and endothelial cells become activated, resulting in the upregulation of adhesion molecules, secretion of cytokines and chemokines and internalization of integrins. Finally, this leads to increased vessel permeability, thereby facilitating leukocyte extravasation as well as fostering a pro-inflammatory environment. Additionally, activated endothelial cells can form migrating tip cells and proliferative stalk cells, resulting in the formation of new blood vessels. Emerging evidence has accumulated indicating that cellular metabolism is crucial in fueling these pro-atherosclerotic processes, including neovascularization and inflammation, thereby contributing to plaque progression and altering plaque stability. Therefore, further research is necessary to unravel the complex mechanisms underlying endothelial cell metabolic changes, and exploit this knowledge for finding and developing potential future therapeutic strategies. In this review we discuss the metabolic alterations endothelial cells undergo in the context of inflammation and atherosclerosis and how this relates to changes in endothelial functioning. Finally, we will describe several metabolic targets that are currently being used for therapeutic interventions.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"3 3","pages":"e210020"},"PeriodicalIF":0.0,"publicationDate":"2021-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38979347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Lipids and Lipoproteins on Hematopoietic Cell Metabolism and Commitment in Atherosclerosis.","authors":"Andrea Baragetti,&nbsp;Fabrizia Bonacina,&nbsp;Alberico Luigi Catapano,&nbsp;Giuseppe Danilo Norata","doi":"10.20900/immunometab20210014","DOIUrl":"https://doi.org/10.20900/immunometab20210014","url":null,"abstract":"<p><p>Hematopoiesis is the process that leads to multiple leukocyte lineage generation within the bone marrow. This process is maintained throughout life thanks to a nonstochastic division of hematopoietic stem cells (HSCs), where during each division, one daughter cell retains pluripotency while the other differentiates into a restricted multipotent progenitor (MPP) that converts into mature, committed circulating cell. This process is tightly regulated at the level of cellular metabolism and the shift from anaerobic glycolysis, typical of quiescent HSC, to oxidative metabolism fosters HSCs proliferation and commitment. Systemic and local factors influencing metabolism alter HSCs balance under pathological conditions, with chronic metabolic and inflammatory diseases driving HSCs commitment toward activated blood immune cell subsets. This is the case of atherosclerosis, where impaired systemic lipid metabolism affects HSCs epigenetics that reflects into increased differentiation toward activated circulating subsets. Aim of this review is to discuss the impact of lipids and lipoproteins on HSCs pathophysiology, with a focus on the molecular mechanisms influencing cellular metabolism. A better understanding of these aspects will shed light on innovative strategies to target atherosclerosis-associated inflammation.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":" ","pages":"e210014"},"PeriodicalIF":0.0,"publicationDate":"2021-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38877320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}