Immunometabolism最新文献

{"title":"T Cell Metabolism in Cancer Immunotherapy.","authors":"Halil-Ibrahim Aksoylar,&nbsp;Natalia M Tijaro-Ovalle,&nbsp;Vassiliki A Boussiotis,&nbsp;Nikolaos Patsoukis","doi":"10.20900/immunometab20200020","DOIUrl":"https://doi.org/10.20900/immunometab20200020","url":null,"abstract":"<p><p>Immune checkpoint therapies aiming to enhance T cell responses have revolutionized cancer immunotherapy. However, although a small fraction of patients develops durable anti-tumor responses, the majority of patients display only transient responses, underlying the need for finding auxiliary approaches. Tumor microenvironment poses a major metabolic barrier to efficient anti-tumor T cell activity. As it is now well accepted that metabolism regulates T cell fate and function, harnessing metabolism may be a new strategy to potentiate T cell-based immunotherapies.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38133108","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":"Multiple Sclerosis: Lipids, Lymphocytes, and Vitamin D.","authors":"Colleen E Hayes, James M Ntambi","doi":"10.20900/immunometab20200019","DOIUrl":"10.20900/immunometab20200019","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. We review the two core MS features, myelin instability, fragmentation, and remyelination failure, and dominance of pathogenic CD4⁺ Th17 cells over protective CD4⁺ Treg cells. To better understand myelin pathology, we describe myelin biosynthesis, structure, and function, then highlight stearoyl-CoA desaturase (SCD) in nervonic acid biosynthesis and nervonic acid's contribution to myelin stability. Noting that vitamin D deficiency decreases SCD in the periphery, we propose it also decreases SCD in oligodendrocytes, disrupting the nervonic acid supply and causing myelin instability and fragmentation. To better understand the distorted Th17/Treg cell balance, we summarize Th17 cell contributions to MS pathogenesis, then highlight how 1,25-dihydroxyvitamin D₃ signaling from microglia to CD4⁺ T cells restores Treg cell dominance. This signaling rapidly increases flux through the methionine cycle, removing homocysteine, replenishing S-adenosyl-methionine, and improving epigenetic marking. Noting that DNA hypomethylation and inappropriate <i>DRB1*1501</i> expression were observed in MS patient CD4⁺ T cells, we propose that vitamin D deficiency thwarts epigenetic downregulation of <i>DRB1*1501</i> and Th17 cell signature genes, and upregulation of Treg cell signature genes, causing dysregulation within the CD4⁺ T cell compartment. We explain how obesity reduces vitamin D status, and how estrogen and vitamin D collaborate to promote Treg cell dominance in females. Finally, we discuss the implications of this new knowledge concerning myelin and the Th17/Treg cell balance, and advocate for efforts to address the global epidemics of obesity and vitamin D deficiency in the expectation of reducing the impact of MS.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38036101","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":"Metabolic Targets for Treatment of Autoimmune Diseases.","authors":"Paramarjan Piranavan,&nbsp;Manjeet Bhamra,&nbsp;Andras Perl","doi":"10.20900/immunometab20200012","DOIUrl":"https://doi.org/10.20900/immunometab20200012","url":null,"abstract":"<p><p>There is a considerable unmet demand for safe and efficacious medications in the realm of autoimmune and inflammatory diseases. The fate of the immune cells is precisely governed by control of various metabolic processes such as mitochondrial oxidative phosphorylation, glycolysis, fatty acid synthesis, beta-oxidation, amino acid metabolism, and several others including the pentose phosphate pathway, which is a unique source of metabolites for cell proliferation and maintenance of a reducing environment. These pathways are tightly regulated by the cytokines, growth factors, availability of the nutrients and host-microbe interaction. Exploring the immunometabolic pathways that govern the fate of cells of the innate and adaptive immune system, during various stages of activation, proliferation, differentiation and effector response, is crucial for new development of new treatment targets. Identifying the pathway connections and key enzymes will help us to target the dysregulated inflammation in autoimmune diseases. The mechanistic target of rapamycin (mTOR) pathway is increasingly recognized as one of the key drivers of proinflammatory responses in autoimmune diseases. In this review, we provide an update on the current understanding of the metabolic signatures noted within different immune cells of many different autoimmune diseases with a focus on selecting pathways and specific metabolites as targets for treatment.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37878196","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":"T cell Metabolism in Lupus.","authors":"Milena Vukelic,&nbsp;Michihito Kono,&nbsp;George C Tsokos","doi":"10.20900/immunometab20200009","DOIUrl":"https://doi.org/10.20900/immunometab20200009","url":null,"abstract":"<p><p>Abnormal T cell responses are central to the development of autoimmunity and organ damage in systemic lupus erythematosus. Following stimulation, naïve T cells undergo rapid proliferation, differentiation and cytokine production. Since the initial report, approximately two decades ago, that engagement of CD28 enhances glycolysis but PD-1 and CTLA-4 decrease it, significant information has been generated which has linked metabolic reprogramming with the fate of differentiating T cell in health and autoimmunity. Herein we summarize how defects in mitochondrial dysfunction, oxidative stress, glycolysis, glutaminolysis and lipid metabolism contribute to pro-inflammatory T cell responses in systemic lupus erythematosus and discuss how metabolic defects can be exploited therapeutically.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37808766","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":"Exposure to Maternal Diabetes in Utero and DNA Methylation Patterns in the Offspring.","authors":"Nancy A West,&nbsp;Katerina Kechris,&nbsp;Dana Dabelea","doi":"10.2478/immun-2013-0001","DOIUrl":"https://doi.org/10.2478/immun-2013-0001","url":null,"abstract":"<p><p>Perturbations in early life environments, including intrauterine exposure to maternal gestational diabetes (GDM), are hypothesized to lead to metabolic imprinting resulting in increased risk of cardiometabolic outcomes later in life. We aimed to 1) identify candidate genes and biological pathways associated with differentially methylated regions (DMRs) in relation to exposure to GDM <i>in utero</i> and, 2) using mediation analysis, more definitively investigate the potential for mediation of the effect of exposure to maternal diabetes <i>in utero</i> on cardiometabolic traits in childhood risk through our identified DMRs. Genome-wide methylation analysis of peripheral blood mononuclear cell's DNA was conducted in 21 healthy children, ages 8-12 years. P-values from multiple linear regression analyses for >27,000 CpG sites were ranked to identify DMRs between the exposure groups. Among the top 10 ranked DMRs, we identified several genes, including NPR1, PANK1, SCAND1, and GJA4, which are known to be associated with cardiometabolic traits. Gene enrichment analysis of the top 84 genes, each with p<=0.005, identified the ubiquitin proteasome system (UPS) as the most enriched biological pathway (p = 0.07). The UPS pathway reflects biological processes known to be associated with endothelial function, inflammation, lipid metabolism, insulin resistance and β-cell apoptosis, whose derangements are central to the pathogenesis of cardiometabolic diseases. Increased methylation of <i>PYGO1</i> and <i>CLN8</i> had the greatest relative mediation effect (RME = 87%, p=0.005 and RME=50%, p=0.01) on the impact of exposure to maternal diabetes <i>in utero</i> on VCAM-1 levels in the offspring. Multiple candidate genes and the UPS were identified for future study as possible links between exposure to maternal gestational diabetes <i>in utero</i> and adverse cardiometabolic traits in the offspring. In particular, increased methylation of <i>PYGO1</i> and <i>CLN8</i> may be biological links between intrauterine exposure to maternal diabetes and significantly increased VCAM-1 levels in the offspring.</p>","PeriodicalId":13361,"journal":{"name":"Immunometabolism","volume":"1 ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2478/immun-2013-0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31577720","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}