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Author: Heather Hartig Pua Publisher: ISBN: Category : Homeostasis Languages : en Pages : 260
Book Description
T cell survival is a carefully regulated processes which impacts T cell development, peripheral homeostasis and immune responses. Although the lysosomally-mediated catabolic process of autophagy was identified decades ago in tissue specimens, only recently has the core molecular machinery responsible for autophagy been identified. An explosion of work has followed characterizing the role of autophagy in metabolism, organelle homeostasis, cell death, oncogenesis, innate immunity, and MHCII cross presentation. Given the emerging role for autophagy in cell survival as well as the critical regulation of death in T lymphocytes, we hypothesized that autophagy plays a novel role in promoting T cell survival in vivo. We found that autophagosomes form in primary T cells, and that the induction of autophagy is regulated in lymphocytes. To test the role of autophagy in T cells, we established two genetic models for the deletion of essential autophagy genes in primary T lymphocytes in vivo. In both Atg5-/- fetal liver chimeras and Atg7f/fLck-Cre mice, T cells developed in the thymus. However, we observed decreased numbers of mature peripheral T cells in naive mice. This reduction in peripheral autophagy-deficient T cell number was associated with an increase in apoptotic cell death. Although autophagy can contribute to the recycling of essential metabolic substrates, we found that autophagy-deficient T cells have intact resting metabolic function and die even in the presence of abundant growth-factor stimulation. A second important function for autophagy in cells is the removal of cytoplasmic material, which may include both proteins and whole organelles. We found that autophagy-deficient T cells have increased mitochondrial content by MitoTracker staining, mitochondrial DNA and mitochondrial proteins. This difference reflects an inability of autophagy-deficient T cells to clear mitochondrial content after cells exit the thymus, a process which normally occurs in autophagy-sufficient cells. Ongoing work seeks to understand the mechanisms by which autophagy-mediated T cell organelle homeostasis contributes to survival through the regulation of ROS production and intrinsic pathway apoptosis.
Author: Heather Hartig Pua Publisher: ISBN: Category : Homeostasis Languages : en Pages : 260
Book Description
T cell survival is a carefully regulated processes which impacts T cell development, peripheral homeostasis and immune responses. Although the lysosomally-mediated catabolic process of autophagy was identified decades ago in tissue specimens, only recently has the core molecular machinery responsible for autophagy been identified. An explosion of work has followed characterizing the role of autophagy in metabolism, organelle homeostasis, cell death, oncogenesis, innate immunity, and MHCII cross presentation. Given the emerging role for autophagy in cell survival as well as the critical regulation of death in T lymphocytes, we hypothesized that autophagy plays a novel role in promoting T cell survival in vivo. We found that autophagosomes form in primary T cells, and that the induction of autophagy is regulated in lymphocytes. To test the role of autophagy in T cells, we established two genetic models for the deletion of essential autophagy genes in primary T lymphocytes in vivo. In both Atg5-/- fetal liver chimeras and Atg7f/fLck-Cre mice, T cells developed in the thymus. However, we observed decreased numbers of mature peripheral T cells in naive mice. This reduction in peripheral autophagy-deficient T cell number was associated with an increase in apoptotic cell death. Although autophagy can contribute to the recycling of essential metabolic substrates, we found that autophagy-deficient T cells have intact resting metabolic function and die even in the presence of abundant growth-factor stimulation. A second important function for autophagy in cells is the removal of cytoplasmic material, which may include both proteins and whole organelles. We found that autophagy-deficient T cells have increased mitochondrial content by MitoTracker staining, mitochondrial DNA and mitochondrial proteins. This difference reflects an inability of autophagy-deficient T cells to clear mitochondrial content after cells exit the thymus, a process which normally occurs in autophagy-sufficient cells. Ongoing work seeks to understand the mechanisms by which autophagy-mediated T cell organelle homeostasis contributes to survival through the regulation of ROS production and intrinsic pathway apoptosis.
Author: Jennifer Lu Publisher: ISBN: 9781321207736 Category : Languages : en Pages : 132
Book Description
Development of functional adaptive and innate immune responses requires strict regulation of programmed cell death signaling pathways. These signaling pathways are essential for shaping and maintaining the immune system, and ensuring functional immune responses. Programmed death is required for clonal deletion of lymphocytes during an infection, and dysregulation results in defective clearance of autoreactive T cells and autoimmune disease. Death Receptor (DR) pathways regulate apoptotic signaling and are essential for immune homeostasis and tolerance. Ligation of DR, CD95/Fas/Apo-1, triggers formation of a cytosolic complex known as the "death-inducing signaling complex" (DISC), which includes adaptor molecule FADD (Fas associated with death domain), Receptor Interacting Protein (RIP) Kinase 1, and caspase-8. Caspase 8 is required for extrinsic apoptosis upon DR ligation, while promoting clonal expansion in T cells following T cell receptor stimulation. In the absence of caspase 8, cells succumb to a programmed necrosis-like death process facilitated by the generation of RIPK1-RIPK3 "necrosomes". The aim of this dissertation is to elucidate the crosstalk between necroptosis and apoptosis in T lymphocytes in the context of caspase 8. By generating RIPK3-/- x FADDdd double mutant mice, we show in Chapter 2 that FADD, caspase 8 and RIP kinases are all essential for clonal expansion, contraction, and antiviral responses. FADDdd T cells also display hyper-autophagy upon activation; thus, another aim of this dissertation is to uncover the role of autophagic signaling in T lymphocytes. Using mice genetically deficient in autophagy protein, Atg5, we demonstrate in Chapter 3 the differential roles for autophagy in naïve and proliferating T cells. Autophagy is required for clearing excess mitochondria in naïve T cells, while activated cells are capable of diluting mitochondria through rapid division. In Chapter 4, we characterize the platform(s) that promote recruitment of RIPK1-RIPK3 complex in T cells by identifying the kinetics, constituency, and subcellular localization of the necrosome. Understanding the paradigms of necroptosis and autophagy and defining the switch between apoptosis and necrosis will allow us to manipulate death pathways to modulate desired immune responses to various diseases and infections.
Author: Beth Levine Publisher: Springer ISBN: 9783642003295 Category : Medical Languages : en Pages : 339
Book Description
Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other forms of stress. It has a growing spectrum of acknowledged roles in immunity, aging, development, neurodegeneration, and cancer biology. An immunological role of autophagy was first recognized with the discovery of autophagy’s ability to sanitize the cellular interior by killing intracellular microbes. Since then, the repertoire of autophagy’s roles in immunity has been vastly expanded to include a diverse but interconnected portfolio of regulatory and effector functions. Autophagy is an effector of Th1/Th2 polarization; it fuels MHC II presentation of cytosolic (self and microbial) antigens; it shapes central tolerance; it affects B and T cell homeostasis; it acts both as an effector and a regulator of Toll-like receptor and other innate immunity receptor signaling; and it may help ward off chronic inflammatory disease in humans. With such a multitude of innate and adaptive immunity functions, the study of autophagy in immunity is one of the most rapidly growing fields of contemporary immunological research. This book introduces the reader to the fundamentals of autophagy, guides a novice and the well-informed reader alike through different immunological aspects of autophagy as well as the countermeasures used by highly adapted pathogens to fight autophagy, and provides the expert with the latest, up-to-date information on the specifics of the leading edge of autophagy research in infection and immunity.
Author: Brian D. Gulbransen Publisher: Biota Publishing ISBN: 1615046615 Category : Medical Languages : en Pages : 72
Book Description
The enteric nervous system (ENS) is a complex neural network embedded in the gut wall that orchestrates the reflex behaviors of the intestine. The ENS is often referred to as the “little brain” in the gut because the ENS is more similar in size, complexity and autonomy to the central nervous system (CNS) than other components of the autonomic nervous system. Like the brain, the ENS is composed of neurons that are surrounded by glial cells. Enteric glia are a unique type of peripheral glia that are similar to astrocytes of the CNS. Yet enteric glial cells also differ from astrocytes in many important ways. The roles of enteric glial cell populations in the gut are beginning to come to light and recent evidence implicates enteric glia in almost every aspect of gastrointestinal physiology and pathophysiology. However, elucidating the exact mechanisms by which enteric glia influence gastrointestinal physiology and identifying how those roles are altered during gastrointestinal pathophysiology remain areas of intense research. The purpose of this e-book is to provide an introduction to enteric glial cells and to act as a resource for ongoing studies on this fascinating population of glia. Table of Contents: Introduction / A Historical Perspective on Enteric Glia / Enteric Glia: The Astroglia of the Gut / Molecular Composition of Enteric Glia / Development of Enteric Glia / Functional Roles of Enteric Glia / Enteric Glia and Disease Processes in the Gut / Concluding Remarks / References / Author Biography
Author: M. A. Hayat Publisher: Academic Press ISBN: 0128094273 Category : Medical Languages : en Pages : 431
Book Description
Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. Presents the most advanced information regarding the role of the autophagic system in life and death Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available
Author: Roberta A. Gottlieb Publisher: Academic Press ISBN: 0123851025 Category : Medical Languages : en Pages : 241
Book Description
Autophagy in Health and Disease offers an overview of the latest research in autophagy with a translational emphasis. This publication takes scientific research in autophagy a step further and offers integrated content with advancements in autophagy from cell biology and biochemical research to clinical treatments. A necessary reference for the bookshelf of medical and scientific researchers and students, Autophagy in Health and Disease presents high quality, reputable information on autophagy, allowing the reader quick access to the most applicable information. Discusses current understanding of the roles of autophagy in health and disease Covers the background of autophagy, the development of tools and therapeutics to measure and modulate autophagy, and autophagy in tissues and disease processes
Author: Jun Cui Publisher: Springer Nature ISBN: 981150606X Category : Medical Languages : en Pages : 203
Book Description
This book discusses novel concepts and discoveries concerning the regulation of innate immunity by autophagy and autophagy-related proteins. In the past decade, there have been major advances in our understanding of the molecular mechanisms of autophagy and its physiological functions. This book highlights emerging studies on the underlying mechanisms of autophagy regulation of innate immunity, including inflammation, antiviral immunity and anti-bacterial responses and the signaling pathways that prompt or inhibit the initiation and progression of related diseases. It also offers new ideas and strategies for future drugs based on manipulating autophagy, especially selective autophagy mediated by cargo receptors. Providing a comprehensive overview of the autophagy regulation of innate immunity, it is a valuable resource for graduate students and researchers in the fields of immunology, cell biology and translational medicine.
Author: Beth Levine Publisher: Springer Science & Business Media ISBN: 3642003028 Category : Medical Languages : en Pages : 345
Book Description
Autophagy is a fundamental biological process that enables cells to autodigest their own cytosol during starvation and other forms of stress. It has a growing spectrum of acknowledged roles in immunity, aging, development, neurodegeneration, and cancer biology. An immunological role of autophagy was first recognized with the discovery of autophagy’s ability to sanitize the cellular interior by killing intracellular microbes. Since then, the repertoire of autophagy’s roles in immunity has been vastly expanded to include a diverse but interconnected portfolio of regulatory and effector functions. Autophagy is an effector of Th1/Th2 polarization; it fuels MHC II presentation of cytosolic (self and microbial) antigens; it shapes central tolerance; it affects B and T cell homeostasis; it acts both as an effector and a regulator of Toll-like receptor and other innate immunity receptor signaling; and it may help ward off chronic inflammatory disease in humans. With such a multitude of innate and adaptive immunity functions, the study of autophagy in immunity is one of the most rapidly growing fields of contemporary immunological research. This book introduces the reader to the fundamentals of autophagy, guides a novice and the well-informed reader alike through different immunological aspects of autophagy as well as the countermeasures used by highly adapted pathogens to fight autophagy, and provides the expert with the latest, up-to-date information on the specifics of the leading edge of autophagy research in infection and immunity.
Author: Heather Hartig Pua
Author: Heather Hartig Pua
Author: Cristina Dumitru
Author: Jennifer Lu
Author: Beth Levine
Author: Agnieszka Martyna Kabat
Author: Brian D. Gulbransen
Author: M. A. Hayat
Author: Roberta A. Gottlieb
Author: Jun Cui
Author: Beth Levine