Metabolism Is Central to Tolerogenic Dendritic Cell Function
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TLDR
It is demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source, which drives differential cellular function and plays a role in pathologies, such as autoimmune disease.Abstract:
Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential.read more
Citations
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Metabolic Control of Dendritic Cell Functions: Digesting Information.
TL;DR: Better understanding of the emerging connection between metabolic adaptions and functional DC specification will likely allow the development of therapeutic strategies to manipulate immune responses, and how metabolism influences DC differentiation and plasticity is relevant.
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Lactate and Immunosuppression in Sepsis.
TL;DR: Recent studies are summarized, showing that the activation of immune cells requires aerobic glycolytic metabolism and that lactate produced by aerobic Glycolysis may play an immunosuppressive role in sepsis.
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3-bromopyruvate ameliorate autoimmune arthritis by modulating Th17/Treg cell differentiation and suppressing dendritic cell activation
TL;DR: 3-bromopyruvate (BrPA), a specific HK2 inhibitor, significantly decreased the arthritis scores and the histological scores in SKG mice, with a significant increase in Treg cells, decrease in Th17 cells, and decrease in activated DCs in the spleen, suggesting that BrPA may be a therapeutic target of murine arthritis.
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STAT3 in Tumor-Associated Myeloid Cells: Multitasking to Disrupt Immunity.
TL;DR: The importance and functional complexity of STAT3 signaling in this immune cell compartment as well as potential strategies for cancer therapy are reviewed.
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Met-Flow, a strategy for single-cell metabolic analysis highlights dynamic changes in immune subpopulations.
Patricia J. Ahl,Patricia J. Ahl,Richard Hopkins,Wen Wei Xiang,Bijin Au,Nivashini Kaliaperumal,Anna-Marie Fairhurst,John E. Connolly,John E. Connolly,John E. Connolly +9 more
TL;DR: Using Met-Flow, a flow cytometry-based method capturing the metabolic state of immune cells by targeting key proteins and rate-limiting enzymes across multiple pathways, it is discovered that glucose restriction and metabolic remodeling drive the expansion of an inflammatory central memory T cell subset.
References
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Journal ArticleDOI
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
TL;DR: Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells and retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+.
Journal ArticleDOI
Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha.
Marie Lagouge,Carmen Argmann,Zachary Gerhart-Hines,Hamid Meziane,Carles Lerin,Frédéric N. Daussin,Nadia Messadeq,Jill C. Milne,Philip D. Lambert,Peter J. Elliott,Bernard Geny,Markku Laakso,Pere Puigserver,Johan Auwerx +13 more
TL;DR: RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in P GC-1alpha acetylation and an increase in PGC-1 alpha activity.
Journal ArticleDOI
PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Cheryl L. Day,Daniel Kaufmann,Photini Kiepiela,Julia A. Brown,Eshia Moodley,Sharon Reddy,Elizabeth W Mackey,Joseph D. Miller,Alasdair Leslie,Chantal DePierres,Zenele Mncube,Jaikumar Duraiswamy,Baogong Zhu,Quentin Eichbaum,Marcus Altfeld,E. John Wherry,Hoosen M. Coovadia,Philip J. R. Goulder,Philip J. R. Goulder,Philip J. R. Goulder,Paul Klenerman,Rafi Ahmed,Gordon J. Freeman,Bruce D. Walker,Bruce D. Walker,Bruce D. Walker +25 more
TL;DR: The data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function.
Journal ArticleDOI
Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression
Chih-Hao Chang,Jing Qiu,David O’Sullivan,Michael D. Buck,Takuro Noguchi,Jonathan D. Curtis,Qiongyu Chen,Mariel Gindin,Matthew M. Gubin,Gerritje J.W. van der Windt,Elena Tonc,Robert D. Schreiber,Edward J. Pearce,Erika L. Pearce +13 more
TL;DR: It is shown that tumor-imposed metabolic restrictions can mediate T cell hyporesponsiveness during cancer, and it is found that blocking PD-L1 directly on tumors dampens glycolysis by inhibiting mTOR activity and decreasing expression of gly colysis enzymes.
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CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms
Richard V. Parry,Jens M. Chemnitz,Kenneth A. Frauwirth,Anthony R. Lanfranco,Inbal Braunstein,Sumire V. Kobayashi,Peter S. Linsley,Craig B. Thompson,James L. Riley +8 more
TL;DR: In this paper, CTLA-4 and PD-1 signaling inhibited Akt phosphorylation by preventing CD3/CD28-mediated upregulation of glucose metabolism and Akt activity, but each accomplished this regulation using separate mechanisms.