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The metabolic challenges of immune cells in health and disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196227 Year: Pages: 80 DOI: 10.3389/978-2-88919-622-7 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-08-16 10:34:25
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Abstract

Obesity and its co-morbidities, including atherosclerosis, insulin resistance and diabetes, are a world-wide epidemic. Inflammatory immune responses in metabolic tissues have emerged as a universal feature of these metabolic disorders. While initial work highlighted the contribution of macrophages to tissue inflammation and insulin resistance, recent studies demonstrate that cells of the adaptive immune compartment, including T and B lymphocytes and dendritic cells also participate in obesity-induced pathogenesis of these conditions. However, the molecular and cellular pathways by which the innate and adaptive branches of immunity control tissue and systemic metabolism remain poorly understood. To engage in growth and activation, cells need to increase their biomass and replicate their genome. This process presents a substantial bioenergetic challenge: growing and activated cells must increase ATP production and acquire or synthesize raw materials, including lipids, proteins and nucleic acids. To do so, they actively reprogram their intracellular metabolism from catabolic mitochondrial oxidative phosphorylation to glycolysis and other anabolic pathways. This metabolic reprogramming is under the control of specific signal transduction pathways whose underlying molecular mechanisms and relevance to physiology and disease are subject of considerable current interest and under intense study. Recent reports have elucidated the physiological role of metabolic reprogramming in macrophage and T cell activation and differentiation, B- and dendritic cell biology, as well as in the crosstalk of immune cells with endothelial and stem cells. It is also becoming increasingly evident that alterations of metabolic pathways play a major role in the pathogenesis of chronic inflammatory disorders. Due to the scientific distance between immunologists and experts in metabolism (e.g., clinicians and biochemists), however, there has been limited cross-talk between these communities. This collection of articles aims at promoting such cross-talk and accelerating discoveries in the emerging field of immunometabolism.

Metabolism and Immune Tolerance

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889457250 Year: Pages: 116 DOI: 10.3389/978-2-88945-725-0 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2019-01-23 14:53:43
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Abstract

Historically the study of the immune system and metabolism have been two very separate fields. In recent years, a growing literature has emerged illustrating how the multiple processes of cellular metabolism are intricately linked to several aspects of immune function and development. This Research Topic covers recent progress in the field now known as “Immunometabolism” and the role of metabolism in immune tolerance. Immune tolerance is operationally defined as a state where a host’s immune system is balanced such that although self-reactive lymphocytes are present, they are kept in check by immune regulation. Perturbations to this homeostasis may result in self-reactive lymphocytes gaining the upper hand and mediating auto-immune disease. Maintenance of immune tolerance involves a large cast of different cell types including effector T cells, regulatory T cells, B cells, stromal cells, dendritic cells and macrophages.Intracellular pathways and individual enzymes of metabolism have been shown to be harnessed by cells of both the adaptive and innate immune system to allow particular immune functions to be achieved. Examples include metabolic enzymes serving ‘moonlighting’ functions in mRNA translation, gene splicing, and kinase activation. Other examples include the requirement for de novo fatty acid synthesis for differentiation into Th17 effectors and CD8 memory T cells or products of the TCA cycle promoting pro-inflammatory cytokine production. Likewise, the availability of extracellular metabolic substrates has a large impact on the maintenance of local immune tolerance. For example, there are different requirements for glucose, glutamine and fatty acids for effector versus regulatory T cell development. Also tolerogenic dendritic cells mediate lowering of extracellular essential amino acids by their enhanced catabolism, promoting the induction of regulatory T cells. The purpose of this Research Topic is to provide an update on the current understanding of the multiple roles for metabolism in regulating the immune system.

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