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Targeting Dendritic Cell Metabolism To Induce Immune Tolerance
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Book Synopsis Targeting Dendritic Cell Metabolism to Induce Immune Tolerance by : Hsi-Ju Wei
Download or read book Targeting Dendritic Cell Metabolism to Induce Immune Tolerance written by Hsi-Ju Wei and published by . This book was released on 2019 with total page 231 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tolerogenic dendritic cells (TolDCs) are actively involved in the elimination of autoreactive T cells in the thymus and quench T cell responses to self-antigens in the periphery under steady state. Normal dendritic cell (DC) maturation is influenced by both the inflammatory milieu and foreign antigens, and is required to generate an immunogenic response. These immunogenic DCs then interact with T and B cells to assist in antibody production. An imbalance between TolDCs and immunogenic DCs may instigate the development of autoimmunity and therefore, TolDCs have emerged as an expedient therapeutic target to manage autoimmunity. Although there is enough scientific evidence available depicting the development and functional utility of TolDCs in preclinical models of autoimmunity, in the absence of a more thorough understanding of TolDC biology their clinical use remains limited. This research work explores the immunomodulatory functions of TolDCs and the discovery of new possible therapeutic targets for the treatment of autoimmunity and provide three major insights. First, the protocol that we established in this thesis will help investigators to evaluate the capacity of new agents to promote the induction of TolDCs and to facilitate the effort to broaden the scope of TolDC therapeutics. Second, our data reveal that DCs are one of the principal cellular mediators of the immunomodulatory responses to the synthetic triterpenoid, CDDO-DFPA, and to related small molecules in the triterpenoid family for which we have shown efficacy in the preclinical model of multiple sclerosis. Third, we report that Nrf2 regulates DC tolerance by modulating their cytokine profile and cellular metabolism. Lastly our data show the therapeutic relevance of targeting Nrf2 signaling in the context of autoimmune disease. These data include analyses of Nrf2 function in preclinical models of multiple sclerosis (MS) and aplastic anemia (AA), and analyses of clinical specimens from patients with aplastic anemia, and together they help to further establish the therapeutic utility of TolDCs in managing clinical manifestations of these diseases. Overall, this is the first systematic research report revealing the Nrf2-dependent mechanisms of DC metabolic reprograming to generate tolerance and highlight their potential therapeutic utility in the treatment of autoimmunity.
Book Synopsis Metabolism and Immune Tolerance by : Duncan Howie
Download or read book Metabolism and Immune Tolerance written by Duncan Howie and published by Frontiers Media SA. This book was released on 2019-01-21 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Book Synopsis Molecular Mechanisms of Dendritic Cell-Mediated Immune Tolerance and Autoimmunity by : Fang Zhou
Download or read book Molecular Mechanisms of Dendritic Cell-Mediated Immune Tolerance and Autoimmunity written by Fang Zhou and published by Frontiers Media SA. This book was released on 2024-04-09 with total page 213 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dendritic cells (DCs) play a critical role in immune system, as they are necessary both for innate and adaptive immunity. According to their function, dendritic cells can be classified in immune tolerogenic or inflammatory DCs. DCs have been shown to regulate T cell-mediated immune responses and lead to immune tolerance and autoimmunity. For example, immune-tolerogenic DCs facilitate the development of regulatory T cells and inhibit T helper 17-mediated autoimmunity in mice with experimental autoimmune encephalomyelitis. Moreover, inflammatory DCs activate CD8+ and CD4+ T cells and elicit T cell-mediated inflammatory immune responses in vivo. However, the molecular and cellular mechanisms underlying DC-mediated immune tolerance and autoimmunity are still obscure.
Book Synopsis Antigen targeting to plasmacytoid dendritic cells by : Jakob Loschko
Download or read book Antigen targeting to plasmacytoid dendritic cells written by Jakob Loschko and published by . This book was released on 2011 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Dendritic Cell Control of Immune Responses by : Penelope Anne Morel
Download or read book Dendritic Cell Control of Immune Responses written by Penelope Anne Morel and published by Frontiers Media SA. This book was released on 2016-07-27 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dendritic cells (DC) are among the first cells to encounter pathogens and damage in peripheral tissues and, upon activation, DC migrate to lymph nodes where they activate and educate T cells to initiate and shape the immune response. DC present pathogen-derived antigen to T cells and drive T cell differentiation into particular effector cells through the expression and secretion of co-stimulatory molecules and cytokines respectively. The study of DC biology has included the identification of multiple DC subsets in tissues and lymphoid organs, the differentiation and plasticity of DC subsets, the functional consequences of DC interaction with pathogen, control of DC migratory properties and the impact of DC on T cell activation and differentiation. In recent years sophisticated systems biology approaches have been developed to deepen our understanding of DC function. These studies have identified differences between DC subsets located in various tissues and critical factors that drive the outcome of the interaction between DC and T cells. DC are currently being used in in various clinical therapeutic settings, including as vaccines for cancer and autoimmune disease. A clear understanding of DC factors that contribute to specific immune responses is vital to the success of DC based therapies. This research topic will give a comprehensive overview of current issues in DC biology and provides an update on the clinical uses of DC in the therapy of autoimmunity and cancer.
Book Synopsis Dendritic Cells by : Michael T. Lotze
Download or read book Dendritic Cells written by Michael T. Lotze and published by . This book was released on 1999 with total page 808 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dendritic Cells is the first definitive book on this subject, and brings together the most current information in the field for scientists and clinicians. It outlines research studies, the first reports of therapeutic applications of dendritic cells, and the enormous potential of these unique cells. Contributors are from the key research groups around the world who are working on the immunobiology of dendritic cells and in applied areas, striving to develop their therapeutic potential.
Book Synopsis Targeting Dendritic Cells for Anti-tumor Immune Responses by : Amanda Kristine Laust
Download or read book Targeting Dendritic Cells for Anti-tumor Immune Responses written by Amanda Kristine Laust and published by . This book was released on 2010 with total page 371 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dendritic cells (DCs) are widely recognized as the most potent antigen-presenting and immunostimulatory cells of the immune system, but they can also play an important immunoregulatory role, maintaining tolerance to self-antigens. These dual roles situate DCs at the root of immunologic functional activity and make DCs extremely attractive reagents for developing immunotherapies against neoplastic and non-neoplastic diseases. My overall goal was to understand DC biology as it pertains to anti-tumor immune responses. To do this, I studied the in vivo targeting of DCs by an alphavirus-based replicon particle vector system (VRP) with native DC tropism in an aggressive rat mammary tumor model. These studies demonstrated that targeting DCs in vivo with VRP encoding the tumor-associated antigen (TAA), rat neu, resulted in 40% treatment efficacy in tumor-bearing animals, down-regulation of neu expression followed by rapid tumor outgrowth in some treated animals, anti-tumor proliferative responses, and CD8+ T cell infiltrates in tumors from VRP-neu treated animals. To improve this efficacy, I hypothesized that targeting multiple TAAs would generate increased anti-tumor activity. I found that targeting rat neu and the TAA, Brother of the Regulator of Imprinted Sites (BORIS), could provide enhanced therapeutic efficacy in tumor-bearing rats. Interestingly, this enhancement was dependent upon the anatomic locations of VRP administration. Although VRP tropism for a DC subset likely plays an important role in its potency, it appears to contribute to the requirement for separate administration sites when targeting multiple TAAs. In vitro systems were also employed to further characterize the VRP-targeted DCs. These studies indicated that a subset of human immature myeloid DCs constitutively expressing IL-32 is the VRP-receptive DC population. Though anti-tumor immune responses and chemotherapeutics can induce cell death via apoptosis and therefore could induce tumor-associated immune suppression, this does not usually occur. Thus, another aim was to utilize in vitro model systems to characterize DC and monocyte/macrophage responses when encountering apoptotic neoplastic cells in the presence of defined complement components, proteins involved in innate immune responses. I showed discrete effects in DCs that were different from autologous monocytes/macrophages. Together, these data represent a promising platform for building more efficacious DC-based immunotherapeutics.
Book Synopsis Mechanisms of Immune Regulation by : Richard D. Granstein
Download or read book Mechanisms of Immune Regulation written by Richard D. Granstein and published by S. Karger AG (Switzerland). This book was released on 1994 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: Among the topics reviewed are T and B cell tolerance, clonal deletion, suppressor cells, mechanisms of immune privileged sites and experimental models of tumor immunity. Oral tolerance, ultraviolet radiation and photosensitized effects on immunity, allograft management, T cell vaccination and regulation of immunity with T cell epitopes are discussed from the point of view of possible therapeutic application.
Book Synopsis The Heterogeneity of Cancer Metabolism by : Anne Le
Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
Book Synopsis Gene Therapy of Autoimmune Disease by : Gerald J. Prud'homme
Download or read book Gene Therapy of Autoimmune Disease written by Gerald J. Prud'homme and published by Springer. This book was released on 2005-07-13 with total page 149 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autoimmune diseases are diverse and responsible for considerable morbidity. Their etiology remains largely unknown, and current therapy with anti-inflammatory drugs is prone to adverse effects, and rarely curative. New therapies with anti-cytokine antibodies or receptors are promising, but require frequent administration of expensive protein drugs. Gene Therapy of Autoimmune Diseases comprehensively reviews research in gene therapy for autoimmune diseases with viral or non-viral vectors. Gene therapy offers the possibility of long-term, continuous delivery of a wide variety of immunosuppressive, anti-inflammatory, or tolerance-inducing agents. Moreover, highly specific genetically modified cells can be produced. This book discusses the most promising avenues in this exciting new field.
Book Synopsis Immune Regulation by : Marc Feldmann
Download or read book Immune Regulation written by Marc Feldmann and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: Leukocyte culture conferences have a long pedigree. This volume records some of the scientific highlights of the 16th such annual con ference, and is a witness to the continuing evolution and popularity of leukocyte culture and of immunology. There is strong evidence of the widening horizons of immunology, both technically, with the obviously major impact of molecular biology into our understanding of cellular processes, and also conceptually. Traditionally, the 'proceedings' of these conferences have been published. But have the books produced really recorded the major part of the conference, the informal, friendly, but intense and some times heated exchanges that take place between workers in tackling very similar problems and systems and which are at the heart of every successful conference? Unfortunately this essence cannot be incorpo rated by soliciting manuscripts. For this reason, we have changed the format of publication, retaining published versions of the symposium papers, but requesting the workshop chairmen to produce a summary of the major new observations and areas of controversy highlighted in their sessions, as a vehicle for defining current areas of interest and debate. Not an easy task, as the workshop topics were culled from the abstracts submitted by the participants, rather than being on predefined topics. The unseasonal warmth in Cambridge was reflected in the atmos phere of the conference, the organization of which benefited from the administrative skills of Jean Bacon, Philippa Wells, Mr. Peter Irving, and Mrs.
Book Synopsis CD4+CD25+ Regulatory T Cells: Origin, Function and Therapeutic Potential by : B. Kyewski
Download or read book CD4+CD25+ Regulatory T Cells: Origin, Function and Therapeutic Potential written by B. Kyewski and published by Springer Science & Business Media. This book was released on 2006-01-09 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: The vertebrate immune system defends the organism against invading pathogens while at the same time being self-tolerant to the body’s own constituents thus preserving its integrity. Multiple mechanisms work in concert to ensure self-tolerance. Apart from purging the T cell repertoire from auto-reactive T cells via negative selection in the thymus dominant tolerance exerted by regulatory T cells plays a major role in tolerance imposition and maintenance. Among the various regulatory/suppressive cells hitherto described, CD4+CD25+ regulatory T cells (Treg) and interleukin-10 producing T regulatory 1 (Tr1) cells have been studied in most detail and are the subject of most articles in this issue. Treg, also called "natural" regulatory T cells, will be traced from their intra-thymic origin to the site of their action in peripheral lymphoid organs and tissues. The repertoire of Treg is clearly biased towards recognition of self-antigens, thereby potentially preventing autoimmune diseases such as gastritis and oophoritis. Regulatory T cells, however also control infections, allergies and tolerance to transplanted tissues and this requires their induction in the periphery under conditions which are not yet fully understood. The concept of dominant tolerance, by far not novel, will offer new insights and hopefully tools for the successful treatment of autoimmune diseases, improved cancer immunotherapy and transplant survival. The fulfillment of these high expectations will, however, require their unambiguous identification and a better understanding of their mode of action.
Book Synopsis Inducing Immune Tolerance to Therapeutic Proteins, Cells and Tissues by : Luis Graca
Download or read book Inducing Immune Tolerance to Therapeutic Proteins, Cells and Tissues written by Luis Graca and published by Frontiers Media SA. This book was released on 2021-12-20 with total page 153 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Signaling Mechanisms Regulating T Cell Diversity and Function by : Jonathan Soboloff
Download or read book Signaling Mechanisms Regulating T Cell Diversity and Function written by Jonathan Soboloff and published by CRC Press. This book was released on 2017-03-27 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: T cells play a vital role mediating adaptive immunity, a specific acquired resistance to an infectious agent produced by the introduction of an antigen. There are a variety of T cell types with different functions. They are called T cells, because they are derived from the thymus gland. This volume discusses how T cells are regulated through the operation of signaling mechanisms. Topics covered include positive and negative selection, early events in T cell receptor engagement, and various T cell subsets.
Download or read book MicroRNA Profiling written by Sweta Rani and published by Springer Nature. This book was released on 2022-11-28 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: This second edition provides updated and comprehensive methods on miRNA biogenesis and their role in the development and progression of various human diseases. Chapters detail miRNA biogenesis, isolating RNA, extracellular vesicles (EVs), circulating miRNAs, analyzing miRNA and miRDeep-P2, protocols for total RNA isolation from cells, cell-derived products, isolation and characterization of exosomes, serum, plasma specimens, and software tools. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, MicroRNA Profiling: Methods and Protocols, Second Edition aims to provide comprehensive and accessible methods to undergraduate, graduate, and established scientist.
Book Synopsis Progress in Cancer Immunotherapy by : Shuren Zhang
Download or read book Progress in Cancer Immunotherapy written by Shuren Zhang and published by Springer. This book was released on 2016-05-30 with total page 293 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides readers an extensive overview of recent progress in basic and clinical research on cancer immunotherapy. Thanks to rapid advances in molecular biology and immunology, it has become increasingly evident that cancer growth is influenced by host immune responses. With the success of a number of clinical trials, immunotherapy has become a promising treatment modality of cancer. This book covers five major topics, including monoclonal antibodies, biological response modifiers, cancer vaccines, adoptive cellular therapy and oncolytic viruses. It also examines the combination of different immune strategies as well as the combination of immunotherapy with other treatments to increase anti-tumor effects. Through the comprehensive discussion of the topic, the book sheds valuable new light on the treatment of tumors.
Book Synopsis Metabolism in Cancer by : Thorsten Cramer
Download or read book Metabolism in Cancer written by Thorsten Cramer and published by Springer. This book was released on 2016-08-24 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.
