Download or read book Lymphocytes in MS and EAE More than just a CD4 World written by Manu Rangachari and published by Frontiers Media SA. This book was released on 2017-10-10 with total page 162 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is degenerative disease of the central nervous system (CNS) in which myelin destruction and axon loss leads to the accumulation of physical, cognitive, and mental deficits. MS affects more than a million people worldwide and managing this chronic disease presents a significant health challenge. Multiple lines of evidence indicate that MS is an autoimmune disorder in which immune cells launch an inflammatory attack targeting myelin antigens. Indeed, myelin-reactive T cells and antibodies have been identified in MS patients and in animal models (namely experimental autoimmune encephalomyelitis, or EAE) that recapitulate many features of human disease. Animal model studies have demonstrated that T cells are both necessary and sufficient to initiate and sustain CNS autoimmunity. However, most MS animal models rely on the role played by CD4+ T cells and partially replicate the multiple aspects of MS pathogenesis. Thus, research in the past has focused heavily on the contribution of CD4+ T cells to the disease process; searching PubMed for “MS AND CD4” yields twice the results as corresponding searches for “CD8” or “B cell” and four times that for “NK cells”. While CD4+ T cells may represent the minimum requirement to mediate CNS autoimmunity, it is clear that the immune response underlying human MS is far more complex and involves numerous other immune cells and subsets. This is well illustrated by the observation that MS patients treated with an anti-CD4 depleting antibody did not gain any clinical benefits whereas removal of several lymphocyte subsets using an anti-CD52 depleting antibody has been shown to impede disease progression. In particular, the pathogenic role(s) of non-CD4+ T cell lymphocytes is relatively poorly understood and under-researched, despite evidence that these subsets contribute to disease pathology or regulation. For example, the observed oligoclonal expansion of CD8+ T cells within the CNS compartment supports a local activation. CD8+ T cells with polarized cytolytic granules are seen in close proximity to oligodendrocytes and demyelinated axons in MS tissues. The presence of B cells in inflammatory lesions and antibodies in the CSF have long been recognized as features of MS and Rituximab, a B cell depleting therapy, has been shown to be highly effective to treat MS. Intriguingly, the putative MS therapeutic reagent Daclizumab may function in part through the expansion of a subset of immunoregulatory NK cells. NKT and γδ T cells may also play a role in CNS autoimmunity, given that they respond to lipid antigens and that myelin is lipid-rich. While different animal models recapitulate some of these aspects of human disease, identifying appropriate models and measures to investigate the role of these less well-understood lymphocytes in MS remains a challenge for the field. This Frontiers research topic aims to create a platform for both animal- and human-focused researchers to share their original data, hypotheses, future perspectives and commentaries regarding the role of these less-well understood lymphocyte subsets (CD8+ T cells, B cells, NK cells, NK T cells, γδ T cells) in the pathogenesis of CNS autoimmunity.
Download or read book Lymphocytes in MS and EAE More Than Just a CD4 World written by and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is degenerative disease of the central nervous system (CNS) in which myelin destruction and axon loss leads to the accumulation of physical, cognitive, and mental deficits. MS affects more than a million people worldwide and managing this chronic disease presents a significant health challenge. Multiple lines of evidence indicate that MS is an autoimmune disorder in which immune cells launch an inflammatory attack targeting myelin antigens. Indeed, myelin-reactive T cells and antibodies have been identified in MS patients and in animal models (namely experimental autoimmune encephalomyelitis, or EAE) that recapitulate many features of human disease. Animal model studies have demonstrated that T cells are both necessary and sufficient to initiate and sustain CNS autoimmunity. However, most MS animal models rely on the role played by CD4+ T cells and partially replicate the multiple aspects of MS pathogenesis. Thus, research in the past has focused heavily on the contribution of CD4+ T cells to the disease process; searching PubMed for "MS AND CD4" yields twice the results as corresponding searches for "CD8" or "B cell" and four times that for "NK cells". While CD4+ T cells may represent the minimum requirement to mediate CNS autoimmunity, it is clear that the immune response underlying human MS is far more complex and involves numerous other immune cells and subsets. This is well illustrated by the observation that MS patients treated with an anti-CD4 depleting antibody did not gain any clinical benefits whereas removal of several lymphocyte subsets using an anti-CD52 depleting antibody has been shown to impede disease progression. In particular, the pathogenic role(s) of non-CD4+ T cell lymphocytes is relatively poorly understood and under-researched, despite evidence that these subsets contribute to disease pathology or regulation. For example, the observed oligoclonal expansion of CD8+ T cells within the CNS compartment supports a local activation. CD8+ T cells with polarized cytolytic granules are seen in close proximity to oligodendrocytes and demyelinated axons in MS tissues. The presence of B cells in inflammatory lesions and antibodies in the CSF have long been recognized as features of MS and Rituximab, a B cell depleting therapy, has been shown to be highly effective to treat MS. Intriguingly, the putative MS therapeutic reagent Daclizumab may function in part through the expansion of a subset of immunoregulatory NK cells. NKT and ?d T cells may also play a role in CNS autoimmunity, given that they respond to lipid antigens and that myelin is lipid-rich. While different animal models recapitulate some of these aspects of human disease, identifying appropriate models and measures to investigate the role of these less well-understood lymphocytes in MS remains a challenge for the field. This Frontiers research topic aims to create a platform for both animal- and human-focused researchers to share their original data, hypotheses, future perspectives and commentaries regarding the role of these less-well understood lymphocyte subsets (CD8+ T cells, B cells, NK cells, NK T cells, ?d T cells) in the pathogenesis of CNS autoimmunity.
Download or read book Recent Advances in the Immunology of Helminth Infection Protection Pathogenesis and Panaceas written by Kara Filbey and published by Frontiers Media SA. This book was released on 2021-05-03 with total page 264 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dr. Paul Giacomin is a co-founder of Paragen Bio. Dr. Siracusa is the founder and president of Nemagen Discoveries. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Download or read book Disease Modifying Therapies in Multiple Sclerosis written by Mahsa Ghajarzadeh and published by Frontiers Media SA. This book was released on 2022-09-30 with total page 287 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Advanced Imaging Methods in Neuroscience written by João O. Malva and published by Frontiers Media SA. This book was released on 2022-01-11 with total page 498 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Innate Immune Responses in CNS Inflammation written by Mireia Guerau-de-Arellano and published by Frontiers Media SA. This book was released on 2021-11-30 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Gut Microbiota Brain Axis in Enteric and Central Neuronal Functions in Health and Neuropsychiatric Disorders written by Francesca Ronchi and published by Frontiers Media SA. This book was released on 2022-06-28 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: Topic Editor Dr. Kasper is co-founder of Symbiotix Biotherapeutics. The other Topic Editors declare no competing interests with regards to the Research Topic theme.
Download or read book Neuroinflammation written by Samuel David and published by John Wiley & Sons. This book was released on 2015-05-26 with total page 321 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuroinflammation has long been studied for its connection to the development and progression of Multiple Sclerosis. In recent years, the field has expanded to look at the role of inflammatory processes in a wide range of neurological conditions and cognitive disorders including stroke, amyotrophic lateral sclerosis, and autism. Researchers have also started to note the beneficial impacts of neuroinflammation in certain diseases. Neuroinflammation: New Insights into Beneficial and Detrimental Functions provides a comprehensive view of both the detriments and benefits of neuroinflammation in human health. Neuroinflammation: New Insights into Beneficial and Detrimental Functions opens with two chapters that look at some fundamental aspects of neuroinflammation in humans and rodents. The remainder of the book is divided into two sections which examine both the detrimental and beneficial aspects of inflammation on the brain, spinal cord and peripheral nerves, on various disease states, and in normal aging. These sections provide a broad picture of the role neuroinflammation plays in the physiology and pathology of various neurological disorders. Providing cross-disciplinary coverage, Neuroinflammation: New Insights into Beneficial and Detrimental Functions will be an essential volume for neuroimmunologists, neurobiologists, neurologists, and others interested in the field.
Download or read book Emerging Drugs and Targets for Multiple Sclerosis written by Ana Martinez and published by Royal Society of Chemistry. This book was released on 2019-06-28 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis (MS) is a complex disease with a presumed autoimmune aetiology and few current effective treatments. Disease modifying therapies focus on the altering the natural course of relapsing and remitting MS, targeting the inflammatory response. Other targets involve tacking the cause of the disease – demyelination of axons through remyelination therapies. Due to several recent breakthroughs in the understanding of the pathophysiology of MS new targets for remyelination and immunomodulation are rapidly emerging. This book provides a comprehensive overview of drug discovery and development for the molecular basis of the disease, from new targets to drugs currently in clinical development, cellular and animal disease models to biomarkers for diagnosis and assessment in clinical trials. Emerging Drugs and Targets for Multiple Sclerosis is an ideal reference for any student or researcher interested in drug development for neurodegenerative diseases, autoimmune diseases and MS in particular.
Download or read book Trending Topics in Multiple Sclerosis written by Alina Gonzalez-Quevedo and published by BoD – Books on Demand. This book was released on 2016-09-08 with total page 340 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by progressive demyelination and neurodegeneration of the central nervous system (CNS), constituting the most common demyelinating disease of the CNS in humans. Although intensive research over many decades has unveiled many pathophysiological mechanisms in the development of MS, the cause is still unknown. Nevertheless, it does seem clear that genetic susceptibility and environmental factors play crucial roles. Trending Topics in Multiple Sclerosis is a book that provides an insight into some of the main problems currently debated in this area of research, focusing on topics that deal with genetic and environmental risk factors, pathophysiological mechanisms, neurocognitive findings, and neuroprotective strategies.
Download or read book Role of Inflammation in Neurodegenerative Diseases written by Maya Koronyo-Hamaoui and published by Frontiers Media SA. This book was released on 2022-07-13 with total page 461 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Multiple Sclerosis and Related Disorders written by Douglas S. Goodin and published by Elsevier. This book was released on 2014-02-05 with total page 734 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple Sclerosis (MS) is generally understood to be an inflammatory autoimmune disease of the central nervous system. While we still are not certain of the root cause of MS, research results suggest that unknown environmental factors and the presence of specific genes seem the most probable targets. MS causes an inflammatory response in the central nervous system leading to neurodegeneration, oligodendrocyte death, axonal damage, and gliosis. Over the past five years ongoing research has greatly expanded our understanding of the pathogenesis of MS, detailed insight into the epidemiology and genetic factors related to MS, the introduction of new technologies and tests to better diagnose and predict the future course of the disease and the introduction of new treatments targeting MS. This collection of review chapters provides a comprehensive reference into the science and clinical applications of the latest Multiple Sclerosis research and will be a valuable resource for the neuroscience research community and the clinical neurology community of researchers and practitioners. A comprehensive tutorial reference detailing our current foundational understanding of Multiple Sclerosis Includes chapters on key topics including the genetics of MS, MRI imaging and MS, and the latest treatment options Each chapter is translational and focuses on current research and impact on diagnosis and treatment options
Download or read book The Epigenetics of Autoimmunity written by Rongxin Zhang and published by Academic Press. This book was released on 2018-04-25 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Epigenetics of Autoimmunity covers a topic directly related to translational epigenetics. Via epigenetic mechanisms, a number of internal and external environmental risk factors, including smoking, nutrition, viral infection and the exposure to chemicals, could exert their influence on the pathogenesis of autoimmune diseases. Such factors could impact the epigenetic mechanisms, which, in turn, build relationship with the regulation of gene expression, and eventually triggering immunologic events that result in instability of immune system. Since epigenetic aberrations are known to play a key role in a long list of human diseases, the translational significance of autoimmunity epigenetics is very high. To bridge the gap between environmental and genetic factors, over the past few years, great progress has been made in identifying detailed epigenetic mechanisms for autoimmune diseases. Furthermore, with rapid advances in technological development, high-throughput screening approaches and other novel technologies support the systematic investigations and facilitate the epigenetic identification. This book covers autoimmunity epigenetics from a disease-oriented perspective and several chapters are presented that provide advances in wide-spread disorders or diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1DM), systemic sclerosis (SSc), primary Sjögren's syndrome (pSS) and autoimmune thyroid diseases (AITDs). These emerging epigenetic studies provide new insights into autoimmune diseases, raising great expectations among researchers and clinicians. This seminal book on this topic comprehensively covers the most recent advances in this exciting and rapidly developing new science. They might reveal not only new clinical biomarkers for diagnosis and disease progression, but also novel targets for potential epigenetic therapeutic treatment. Provides the accurate and cutting-edge information on autoimmunity epigenetics Wide coverage appeals to those interested in fundamental epigenetics and inheritance to those with more clinical interests Critical reviews of the mean of deriving and analysing autoimmunity epigenetics information as well as its translational potential Up-to-date coverage of emerging topics in autoimmunity epigenetics
Download or read book Modulation of the OGF OGFr Axis Alters the Disease Course of Relapse Remitting Experimental Autoimmune Encephalomyelitis written by Leslie Hammer and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is a chronic autoimmune disease of the central nervous system and affects over 2.3 million individuals worldwide. The etiology of MS is unknown. However, epidemiological evidence suggests a combination of environmental and genetic factors. No cure exists for MS. Current FDA-approved therapies target limited aspects of the disease, are expensive, and have undesirable side-effects. Experimental autoimmune encephalomyelitis (EAE) is the most widely used animal model for MS. EAE is a CD4+ T cell disease that can be induced in mice through immunization with a myelin antigen, such as proteolipid protein (PLP139-151) in EAE susceptible mice like the SJL/J-strain. Modulation of the opioid growth factor (OGF)-opioid growth factor receptor (OGFr) axis, by administration of OGF or low dose naltrexone (LDN), in both chronic and/or chronic established EAE diminishes disease severity and reduces the histopathological damage associated with the disease. This holds promise for those patients who experience the progressive form of the disease; however, 85 percent of MS patients experience the relapse-remitting disease course. It is unknown whether OGF and/or LDN will be an effective treatment option for RR-MS patients. The central hypothesis is that modulation of the OGF-OGFr axis alters the course of relapse-remitting EAE (RR-EAE). The objectives of this research were to establish a working model of RR-EAE utilizing immunization of the SJL/J mouse with PLP139-151 and to assess the safety and efficacy of LDN or OGF when treatment is initiated at the time of induction or at the time of established clinical disease. Behavior and morphology of glia, macrophages, and neurons were evaluated, as well as the effects of treatment regiments on CD4+ T lymphocyte infiltration into the CNS.The first study established an animal model for relapse-remitting experimental autoimmune encephalomyelitis by immunization of SJL/J mice with PLP139-151. Treatment with OGF or saline was initiated simultaneously with immunization, and within 9 days, behavioral signs of RR-EAE were observed. OGF-treated RR-EAE animals had less severe clinical disease than mice receiving saline and exhibited 66% reductions in median cumulative disease scores, as well as prolonged periods of remission and diminished number and length of disease relapses. Neuropathological examination of lumbar spinal cord revealed reduced numbers of Iba-1 and CD3+ reactive cells, suggesting that OGF inhibited proliferation of microglia/macrophages and T lymphocytes, as well as decreasing the number of proliferating activated astrocytes (Ki67 and GFAP staining). Areas of demyelination and neuronal damage were markedly reduced after the 55-day observation period. The second study examined the therapeutic efficacy of OGF in an established RR-EAE model. Two days following establishment of clinical disease, treatment with OGF or saline was initiated, and mice were observed on a daily basis. OGF treated mice had markedly reduced clinical signs of disease over the course of 40 days. OGF treatment increased the incidence and lengthened the time of remissions relative to saline-treated mice with RR-EAE. OGF therapy also reduced relapses, and facilitated extended periods of mild disease. Neuropathological examination of lumbar spinal cord after 40 days of treatment revealed decreased numbers of Iba-1 and CD3+ reactive cells, suggesting that OGF inhibited proliferation of microglia/macrophages and T lymphocytes, as well as decreasing the number of proliferating activated astrocytes (Ki67 and GFAP dual labeled sections). Peptide treatment for 40 days diminished levels of demyelination in comparison to saline-treated mice with RR-EAE.The third study examined modulation of the OGF-- OGFr axis by low dose naltrexone (LDN) as a disease modifying therapy for established RR-EAE. After two days of clinical disease, mice received LDN or saline for 40 days. Mice were euthanized at study endpoints and spinal cords collected for neuropathological evaluation of glia, T lymphocyte infiltration, and demyelination. LDN treatment significantly reduced behavior scores across the 40 day observation period. The number of remissions was increased in LDN-treated groups relative to controls. A bimodal distribution of behavioral responses to LDN distinguished "responders" from mice considered "non-responders" that showed behavioral characteristics similar to saline-treated animals. More than 60% of the mice responding to LDN displayed several days of remission. LDN-treated mice also had reduced areas of demyelination and decreased numbers of macrophages/microglia and activated astrocytes, as well as reductions in spinal cord demyelination, relative to saline-treated controls. The fourth study examined whether OGF or LDN alter Th effector responses of CD4+ T lymphocytes within the CNS in established EAE. SJL/J mice were immunized with PLP139-151 and treated with OGF, LDN or saline after the second consecutive day of clinical disease. After five treatment days, EAE mice were euthanized and brains and spinal cords collected for intracellular staining. Mononuclear cells were stained were surface stained with anti-CD4, followed by intracellular and transcription factor staining with antibodies for IFN[gamma], IL-17, IL-4 and Foxp3 in order to assess the presence of CD4+ Th1, Th17, Th2, and Treg effector cells in the CNS. Flow cytometry analysis demonstrated that OGF and not LDN decreased CD4+ T lymphocytes present in the CNS of SJL/J mice with EAE at peak disease. However, modulation of the OGF-OGFr axis did not result in changes to CD4+ Th effector cell responses.In conclusion, the data from these studies demonstrate an active role for endogenous opioids in autoimmune diseases such as MS and EAE. Furthermore, these results support previous research indicating that modulation of the OGF-OGFr axis, through either exogenous OGF or intermittent blockade with LDN, can be safe and effective treatment options for EAE and MS. Of particular interest were the opposing effects of OGF and LDN on CD4+ T lymphocytes present in the CNS of established EAE mice, and the lack of effect on different effector cell subpopulations. These results add to the knowledge previously elucidated from studies using the chronic-EAE model, and have opened the door to ongoing research to discern the mechanisms behind OGF and LDN in animal models of EAE, and ultimately the pursuit of clinical trials on OGF and/or LDN for treating MS.
Download or read book Translational Neuroimmunology in Multiple Sclerosis written by Ruth Arnon and published by Academic Press. This book was released on 2016-05-10 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis (MS) is the most common disabling neurological disease of young adults. More than 2.3 million people are affected by MS worldwide. Symptoms can vary widely, depending on the localization and amount of the damage induced by combined inflammatory, demyelinating, and neurodegenerative processes. Although a cure for MS does not currently exist, therapies can help treat MS attacks, attenuate disease activity, reduce progress of the disease, and manage symptoms. Translational Neuroimmunology in Multiple Sclerosis provides an overview of recent findings and knowledge of the neuroimmunology of multiple sclerosis, from experimental models and the human disease to the translation of this research to immunotherapeutic strategies. Chapters describe genetic and environmental factors underlying the disease pathogenesis of MS as a basis for development of immunotherapies, immunological markers of disease activity, pharmacogenetics, and responses to therapy. Immunomodulatory therapies currently in practice and future therapeutic strategies on the horizon—such as neuroprotective strategies, stem cells, and repair promotion—are discussed. Contributed by renowned leaders in the field, this cross-disciplinary volume is a great resource for basic scientists and clinical practitioners in neuroscience, neurology, immunology, pharmacology, and in-drug development. Provides an overview of recent findings and knowledge of the neuroimmunology of multiple sclerosis and the translation of this research to immunotherapy treatment Edited by renowned leaders in the field of neuroimmunology and multiple sclerosis Contains the latest resource material for basic and clinical scientists and practitioners in neuroscience, neurology, immunology, and pharmacology
Download or read book The Interplay of Microbiome and Immune Response in Health and Diseases written by Gwendolyn Barcel´o-Coblijn and published by MDPI. This book was released on 2019-11-06 with total page 206 pages. Available in PDF, EPUB and Kindle. Book excerpt: [Increasing evidence suggests that microbiota and especially the gut microbiota (the microbes inhabiting the gut including bacteria, archaea, viruses, and fungi) plays a key role in human physiology and pathology. Recent findings indicate how dysbiosis—an imbalance in the composition and organization of microbial populations—could severely impact the development of different medical conditions (from metabolic to mood disorders), providing new insights into the comprehension of diverse diseases, such as IBD, obesity, asthma, autism, stroke, diabetes, and cancer. Given that microbial cells in the gut outnumber host cells, microbiota influences human physiology both functionally and structurally. Microbial metabolites bridge various—even distant—areas of the organism by way of the immune and hormone system. For instance, it is now clear that the mutual interaction between the gastrointestinal tract and the brain (gut–brain axis), often involves gut microbiota, indicating that the crosstalk between the organism and its microbial residents represents a fundamental aspect of both the establishment and maintenance of healthy conditions. Moreover, it is crucial to recognize that beyond the intestinal tract, microbiota populates other host organs and tissues (e.g., skin and oral mucosa). We have edited this eBook with the aim of publishing manuscripts focusing on the impact of microbiota in the development of different diseases and their associated treatments.]
Download or read book Myeloid Derived Suppressor Cells as Disease Modulators written by Olivera J. Finn and published by Frontiers Media SA. This book was released on 2020-05-06 with total page 162 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myeloid Derived Suppressor Cells (MDSCs) are a heterogeneous population of immature myeloid cells that can suppress the function of multiple immune cells and in particular, T cells, through various mechanisms. MDSCs can be divided into two major subtypes based on their cell surface phenotype and morphology: polymorphonuclear MDSC (PMN-MDSC or G-MDSC) and monocytic MDSC (M-MDSC). Additional subtypes have been proposed, such as the early MDSC (e-MDSC) that lack both macrophage and granulocyte markers. There is still considerable ambiguity about the phenotype of these cells that corresponds to their immunosuppressive function and there are on-going challenges on how to identify, purify and/or potentially generate and expand these cells in vitro. MDSCs were first discovered in cancer patients where they have been most extensively studied as components of the immunosuppressive tumor microenvironment. In the last several years, however, the importance of their immunomodulatory role in many other disease and clinical settings has emerged. Acknowledgments We acknowledge the initiation and support of this Research Topic by the International Union of Immunological Societies (IUIS). We hereby state publicly that the IUIS has had no editorial input in articles included in this Research Topic, thus ensuring that all aspects of this Research Topic are evaluated objectively, unbiased by any specific policy or opinion of the IUIS.
