Mechanisms Of Pregnancy Induced Tolerance In An Animal Model Of Multiple Sclerosis
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Effects Of Pregnancy And Hormones On T Cell Immune Regulation In Multiple Sclerosis
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Author : Sandra Hellberg
language : en
Publisher: Linköping University Electronic Press
Release Date : 2019-10-22
Effects Of Pregnancy And Hormones On T Cell Immune Regulation In Multiple Sclerosis written by Sandra Hellberg and has been published by Linköping University Electronic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-10-22 with categories.
Multiple sclerosis (MS) is characterized by a dysregulated immune system leading to chronic inflammation in the central nervous system. Despite increasing number of treatments, many patients continue to deteriorate. A better understanding of the underlying disease mechanisms involved in driving disease is a pre-requisite for finding new biomarkers and new treatment targets. The improvement of MS during pregnancy, comparable to the beneficial effects of the most effective treatment, suggests that the transient and physiological immune tolerance established during pregnancy could serve as a model for successful immune regulation. Most likely the immune-endocrine alterations that take place during pregnancy to accommodate the presence of the semi-allogenic fetus contribute to the observed disease improvement. The aim of this thesis was to characterize the dysregulated immune system in MS and define potential factors and mechanisms established during pregnancy that could be involved in the pregnancy-induced effects in MS, focusing on CD4+ T cells as one of the main drivers in immunity and in the MS pathogenesis. Using a network-based modular approach based on gene expression profiling, we could show that CD4+ T cells from patients with MS displayed an altered dynamic gene response to activation, in line with a dysregulated immune system in MS. The resulting gene module disclosed cell activation and chemotaxis as central components in the deviating response, results that form a basis for further studies on its modulation during pregnancy. Moreover, a combination of secreted proteins (OPN+CXCL1-3+CXCL10-CCL2), identified from the module, could be used to separate patients and controls, predict disease activity after 2 years and discriminate between high and low responders to treatment, highlighting their potential use as biomarkers for predicting disease activity and response to treatment. The pregnancy hormone progesterone (P4), a potential factor involved in the pregnancy-induced amelioration of MS, was found to significantly dampen CD4+ T cell activation. Further detailed transcriptomic profiling revealed that P4 almost exclusively down-regulated immune-related pathways in activated T cells, several related to or downstream of T cell activation such as JAKSTAT signaling, T cell receptor signaling and cytokine-cytokine receptor interaction. In particular, P4 significantly affected genes of relevance to diseases known to be modulated during pregnancy, where genes associated to MS were most significantly affected, supporting a role for P4 in the pregnancy-induced immunomodulation. By using another approach, the role of thymus in T cell regulation during pregnancy was assessed. Two established measures of thymic output, CD31 expression and TREC content, were used and showed that thymic output of T cells is maintained during human pregnancy, or even possibly increased in terms of regulatory T cells. This thesis further supports a pivotal role for CD4+ T cells and T cell activation in the MS pathogenesis and adds to the knowledge of how they could be involved in driving disease. We identified a novel strategy for capturing central aspects of the deviating response to T cell activation that could be translated into potentially clinically relevant biomarkers. Further, P4 is emerging as a promising candidate for the pregnancy-induced immunomodulation that could be of importance as a future treatment option. Lastly, maintained thymic output of T cells during human pregnancy challenges the rodent-based dogma of an inactive thymus during pregnancy. Thymic dysfunction has been reported not only in MS but also in rheumatoid arthritis, another inflammatory disease that improves during pregnancy, which highlights a potential role for thymus in immune regulation that could be involved in the pregnancy-induced amelioration.
Multiple Sclerosis
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Author : Institute of Medicine
language : en
Publisher: National Academies Press
Release Date : 2001-08-10
Multiple Sclerosis written by Institute of Medicine and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001-08-10 with Medical categories.
Multiple sclerosis is a chronic and often disabling disease of the nervous system, affecting about 1 million people worldwide. Even though it has been known for over a hundred years, no cause or cure has yet been discovered-but now there is hope. New therapies have been shown to slow the disease progress in some patients, and the pace of discoveries about the cellular machinery of the brain and spinal cord has accelerated. This book presents a comprehensive overview of multiple sclerosis today, as researchers seek to understand its processes, develop therapies that will slow or halt the disease and perhaps repair damage, offer relief for specific symptoms, and improve the abilities of MS patients to function in their daily lives. The panel reviews existing knowledge and identifies key research questions, focusing on: Research strategies that have the greatest potential to understand the biological mechanisms of recovery and to translate findings into specific strategies for therapy. How people adapt to MS and the research needed to improve the lives of people with MS. Management of disease symptoms (cognitive impairment, depression, spasticity, vision problems, and others). The committee also discusses ways to build and financially support the MS research enterprise, including a look at challenges inherent in designing clinical trials. This book will be important to MS researchers, research funders, health care advocates for MS research and treatment, and interested patients and their families.
Research Awards Index
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Author :
language : en
Publisher:
Release Date : 1988
Research Awards Index written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1988 with Medicine categories.
Immune Modulatory Effects Of Vitamin D
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Author : Susu M. Zughaier
language : en
Publisher: Frontiers Media SA
Release Date : 2020-12-16
Immune Modulatory Effects Of Vitamin D written by Susu M. Zughaier and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-12-16 with Medical categories.
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Research Grants Index
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Author : National Institutes of Health (U.S.). Division of Research Grants
language : en
Publisher:
Release Date : 1975
Research Grants Index written by National Institutes of Health (U.S.). Division of Research Grants and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1975 with Medicine categories.
Primate Models Of Children S Health And Developmental Disabilities
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Author : Thomas Burbacher
language : en
Publisher: Academic Press
Release Date : 2011-10-10
Primate Models Of Children S Health And Developmental Disabilities written by Thomas Burbacher and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-10-10 with Medical categories.
The rate of neurodevelopmental disabilities, including autism, mental retardation, hearing loss and attention deficit hyperactivity disorder is rising in the United States. Although estimates of the prevalence of these disorders vary, figures from the CDC indicate that 4% of all school age children are developmentally disabled. During infancy, many important milestones in behavioral development are shared between human and nonhuman primates. Learning more about the causes of abnormal development in monkeys has provided important insights into the mechanisms underlying neurodevelopmental disabilities in human infants. This book documents the latest research not commonly found in other references, and provides a comprehensive look at the results from decades of work with nonhuman primates as it relates to child development and disability. Includes hot topics such as early chemical exposures, immunological influences on development, low birth weight, endocrine disrupters, pediatric AIDS, origin of childhood psychopathologies and assisted reproductive technology Represents the significant body of work accumulated since funding for research on developmental disabilities has increased substantially in recent years
Biomedical Index To Phs Supported Research
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Author :
language : en
Publisher:
Release Date : 1988
Biomedical Index To Phs Supported Research written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1988 with Medicine categories.
Biomedical Index To Phs Supported Research Pt A Subject Access A H
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Author :
language : en
Publisher:
Release Date : 1992
Biomedical Index To Phs Supported Research Pt A Subject Access A H written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1992 with Medicine categories.
Obstetrics By Ten Teachers
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Author : Louise C Kenny
language : en
Publisher: CRC Press
Release Date : 2017-05-18
Obstetrics By Ten Teachers written by Louise C Kenny and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-05-18 with Medical categories.
First published in 1917 as 'Midwifery', Obstetrics by Ten Teachers is well established as a concise, yet comprehensive, guide within its field. The twentieth edition has been thoroughly updated by a new team of 'teachers', integrating clinical material with the latest scientific developments that underpin patient care. Each chapter is highly structured, with learning objectives, definitions, aetiology, clinical features, investigations, treatments, case histories and key point summaries and additional reading where appropriate. New themes for this edition include 'professionalism' and 'global health' and information specific to both areas is threaded throughout the text. Along with its companion Gynaecology by Ten Teachers the book will continue to provide an accessible 'one stop shop' in obstetrics and gynaecology for a new generation of doctors.
Vitamin D
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Author : David Feldman
language : en
Publisher: Academic Press
Release Date : 2011-05-12
Vitamin D written by David Feldman and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-05-12 with Medical categories.
Vitamin D, a steroid hormone, has mainly been known for its effects on bone and osteoporosis. The current therapeutic practices expand into such markets as cancer research, pediatrics, nephrology, dermatology, immunology, and genetics. This 3e includes over 100 chapters covering everything from chemistry and metabolism to mechanisms of action, diagnosis and management, new analogs, and emerging therapies. This complete reference works is a must-have resource for anyone working in endocrinology, osteology, bone biology, or cancer research. *Most comprehensive, up-to-date two-volume set on Vitamin D *Initial chapters cover the chemistry and metabolism of vitamin D, role in mineralization, other target organs, and general physiological effects *Second volume is more clinically oriented addressing deficiency problems (including diagnosis, interactions in the endocrine system, and involvement in malignancies) *Further sections on emerging uses for treatments of auto-immune diseases and diabetes *New chapters on squamous cell cancer, brain cancer, thyroid cancer and many more *Over 600 illustrations and figures available on CD