Immunometabolism And Metabolic Reprogramming Of Immune Cells In Human Physiology And Disease

Immunometabolism has emerged as an intersectional crossroad between metabolism and immune response. Over the past decade, it has become clear that most - if not all - immune cell functions are not separated from cellular metabolism. Although seminal works have addressed the metabolic fate of immune cells during differentiation and function, the physiological status of a given tissue is also dependent on the cell metabolism. The dialogue between immune cells and their microenvironment can also modulate cellular metabolism, which can trigger the onset and progression of a multitude of inflammation-mediated diseases. Thus, uncovering the specific characteristics of the metabolism in different immune cells types and in different conditions, can shed light into the molecular mechanisms of disease and help develop new drugs and therapeutic strategies to treat immune diseases. The edited volume Essentials aspects of Immunometabolism will give the readers a broad view on how metabolic pathways can influence many types of immune cells during activation, differentiation and function, in health and disease. Of note, the structure of the book was created thinking not only on the experienced immunologist but also on undergraduate and graduate students, physicians, and all members of the scientific community interested in this exciting field of research.

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.

This book offers a broad overview of the concepts and research findings in immunometabolism. The immune system is made up of numerous different cell types, pathways, and components that must be able to respond rapidly to a pathogen or cancer, but must also remain quiescent in the absence of challenges. Immune cells rely on metabolic pathways to adapt to changing environments and stimuli. Additionally, these cells can be modified in function or fate by fluctuations in available nutrients. The chapters in this book describe ways in which immune cells utilize and are regulated by metabolic pathways. Topics include how immune-cell metabolism shapes immune homeostasis, and how dysregulation of these pathways can lead to immune disorders. In different contexts, such as a tumor microenvironment, immune-cell function and identity may be modified not only by cytokines and checkpoint molecules, but also by nutrient availability and other metabolic stimuli. Transcriptional reprogramming confers many of the changes in immune cell metabolism that are seen when a T-cell, for example, undergoes activation or functional adaptation to different environments. Lastly, immune cells can destructively or protectively participate in human metabolic homeostasis or disorders. This book summarizes immune-metabolism from a variety of different perspectives, including the ways in which metabolic cues, pathways, and requirements of immune cells change in conditions of homeostasis and activation. The exploration of the significance of metabolic checkpoints and other cues, particularly in the context of cancer and immune disorders, may form the foundation for the development of therapeutics.

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.

This detailed book showcases the tremendous effort and progress made in developing techniques and protocols for the study of immunometabolism, and in utilizing recent technological advances for probing and manipulating adipose and immune cells, and subsequently, their functions and immunometabolic consequences. Written by experts in the field, many chapters use macrophages as a model immune cell type, due to their prominence in the innate immune system and the exhaustive study of their traits. Protocols using adipocytes, dendritic cells, and T cells as model cell lines, as well as measurement of glucose metabolism at the systemic level, have also been included. Written for the highly successful Methods in Molecular Biology book series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Immunometabolism: Methods and Protocols serves as a vital guide for researchers working at the important interface of immunology and metabolism.

Get a quick, expert overview of the latest clinical information and guidelines for cancer checkpoint inhibitors and their implications for specific types of cancers. This practical title by Drs. Fumito Ito and Marc Ernstoff synthesizes the most up-to-date research and clinical guidance available on immune checkpoint inhibitors and presents this information in a compact, easy-to-digest resource. It’s an ideal concise reference for trainee and practicing medical oncologists, as well as those in research. Discusses the current understanding of how to best harness the immune system against different types of cancer at various stages. Helps you translate current research and literature into practical information for daily practice. Presents information logically organized by disease site. Covers tumor immunology and biology; toxicities associated with immune checkpoint inhibitors; and future outlooks. Consolidates today’s available information on this timely topic into one convenient resource.