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Author: Steven Schaffert Publisher: ISBN: Category : Languages : en Pages :
Book Description
Much has been learned about the molecular and cellular components critical for the control of immune responses and tolerance. It remains a challenge, however, to control the immune response and tolerance at the system level without causing significant toxicity to normal tissues. Recent studies suggest that microRNAs (miRNAs), an abundant class of ~22 nucleotides regulatory RNAs, play important roles in immune cells. In this thesis, I examined the function of miR-181 genes in regulating T cell selection, development, and immune tolerance. We show that genetic ablation of mir-181a-1/b-1 -- a T cell sensitivity tuner -- in double-positive (DP) thymocytes dampens TCR and Erk signaling and affects positive selection. Moreover, dampening TCR signaling as the result of mir-181a-1/b-1 deletion potentiates the reactivity of self-specific T cells without significantly affecting the pool sizes of naive T cells recognizing specific self-antigens. Finally, loss of mir-181a-1/b-1 in peripheral T cells reduces their basal TCR signaling and their ability to migrate from lymph nodes to the pathogenic sites during autoimmune perturbations. Interestingly, loss of mir-181a-1/b-1 results in quantitative defects in various T and B lymphocyte populations, but does not cause major structural damage to the immune system or spontaneous autoimmunity. Our findings illustrate that mir-181a-1/b-1 controls tolerance through opposing activities in selection and peripheral T cell function. Thus, despite the subtle effects of miRNAs on gene expression, miRNAs have the potential to influence the outcomes of normal and pathogenic immune responses by controlling the quantitative and dynamic aspects of immune responses.
Author: Steven Schaffert Publisher: ISBN: Category : Languages : en Pages :
Book Description
Much has been learned about the molecular and cellular components critical for the control of immune responses and tolerance. It remains a challenge, however, to control the immune response and tolerance at the system level without causing significant toxicity to normal tissues. Recent studies suggest that microRNAs (miRNAs), an abundant class of ~22 nucleotides regulatory RNAs, play important roles in immune cells. In this thesis, I examined the function of miR-181 genes in regulating T cell selection, development, and immune tolerance. We show that genetic ablation of mir-181a-1/b-1 -- a T cell sensitivity tuner -- in double-positive (DP) thymocytes dampens TCR and Erk signaling and affects positive selection. Moreover, dampening TCR signaling as the result of mir-181a-1/b-1 deletion potentiates the reactivity of self-specific T cells without significantly affecting the pool sizes of naive T cells recognizing specific self-antigens. Finally, loss of mir-181a-1/b-1 in peripheral T cells reduces their basal TCR signaling and their ability to migrate from lymph nodes to the pathogenic sites during autoimmune perturbations. Interestingly, loss of mir-181a-1/b-1 results in quantitative defects in various T and B lymphocyte populations, but does not cause major structural damage to the immune system or spontaneous autoimmunity. Our findings illustrate that mir-181a-1/b-1 controls tolerance through opposing activities in selection and peripheral T cell function. Thus, despite the subtle effects of miRNAs on gene expression, miRNAs have the potential to influence the outcomes of normal and pathogenic immune responses by controlling the quantitative and dynamic aspects of immune responses.
Author: Bruce Spiegelman Publisher: Springer ISBN: 3319727907 Category : Science Languages : en Pages : 108
Book Description
The world is faced with an epidemic of metabolic diseases such as obesity and type 2 diabetes. This is due to changes in dietary habits and the decrease in physical activity. Exercise is usually part of the prescription, the first line of defense, to prevent or treat metabolic disorders. However, we are still learning how and why exercise provides metabolic benefits in human health. This open access volume focuses on the cellular and molecular pathways that link exercise, muscle biology, hormones and metabolism. This will include novel “myokines” that might act as new therapeutic agents in the future.
Author: Jiayi Dong Publisher: ISBN: Category : Languages : en Pages : 88
Book Description
MicroRNAs (miRNAs), a class of small non-coding RNA molecules, are key nodes in regulatory networks that fine-tune gene expression and orchestrate diverse signaling pathways that shape immune responses. Since the first study of Dicer-dependent miRNA pathway in regulatory T (Treg) cells in more than a decade ago, miRNAs have been shown to serve as key regulatory elements in controlling the development and function of this specialized CD4+ T cell subset that is indispensable for maintaining immune tolerance and homeostasis. Nevertheless, despite the rapidly accumulating knowledge of the role of miRNAs in Treg cells, our understanding of the intricate regulations of miRNAs and their targets in regulating different aspects of Treg cell biology remains limited. In this work, we demonstrate a critical role for miR-155, which ensures proper Treg cell development in the thymus. Specifically, in addition to the previously reported function of miR-155 in conferring Treg cell competitive fitness, we uncover a novel miR-155-TGF[beta] axis in the thymic medulla that determines medullary thymic epithelial cell (mTEC) maturity and, consequently, the quantity of thymic Treg cells. In addition to miR-155, we also identify another miRNA family, miR-15/16 that plays an important role in restricting Treg cell function and homeostasis. To this end, we find that the miR-15/16 family, miR-15b/16-2 in particular, is specifically up-regulated in Treg cells in the thymus. Nevertheless, this miRNA family does not seem to play a significant role in regulating thymic Treg cell development. Rather, it is important to control effector Treg (eTreg) cell differentiation and function in the periphery. Mechanistically, the miR-15/16 family targets a network of genes, including a transcription factor, IRF4 that are critical for the establishment of the eTreg cell program. Collectively, our findings highlight both cell-extrinsic and -intrinsic roles of miRNAs mediated by miR-155 and miR-15/16, respectively in controlling Treg cell biology. Our work not only reveals novel mechanisms by which miRNAs regulate Treg cell-mediated immune tolerance but also provides molecular insights that will undoubtedly aid in developing innovative strategies targeting Treg cells to treat a wide range of immunological disorders.
Author: Ronald Trent Publisher: Humana ISBN: 9781493947003 Category : Science Languages : en Pages : 0
Book Description
In Clinical Bioinformatics, Second Edition, leading experts in the field provide a series of articles focusing on software applications used to translate information into outcomes of clinical relevance. Recent developments in omics, such as increasingly sophisticated analytic platforms allowing changes in diagnostic strategies from the traditional focus on single or small number of analytes to what might be possible when large numbers or all analytes are measured, are now impacting patient care. Covering such topics as gene discovery, gene function (microarrays), DNA sequencing, online approaches and resources, and informatics in clinical practice, this volume concisely yet thoroughly explores this cutting-edge subject. 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 easily accessible, Clinical Bioinformatics, Second Edition serves as an ideal guide for scientists and health professionals working in genetics and genomics.
Author: Nik Sheng Ding Publisher: Springer ISBN: 3030114465 Category : Medical Languages : en Pages : 355
Book Description
This book provides a comprehensive and complete overview of biomarkers in clinical practice for inflammatory bowel disease (IBD) bringing together the literature in a clear and concise manner. The book bridges the gap between growing knowledge at the bench and current and future applications of biomarkers in clinical practice. The central structure of the book focuses on prognostic and predictive biomarkers in IBD with an emphasis on the fields of research and scientific techniques (genomics, proteomics and metabonomics) that have led to biomarker discovery and places these biomarkers within a clinical context to help understand their utility in clinical practice. This book will be of use to clinicians who have an interest in using biomarkers in clinical practice as well as clinician researchers and scientists involved in the biomarker research pipeline. The author team comprises experts from around the world in order to bring together the literature in an effort to inform clinicians and researchers about the current state-of-the art in biomarker discovery. It is intended to assist future research efforts and indicate how biomarkers might be best applied to clinical practice both at present and in the future.
Author: Publisher: Academic Press ISBN: 012803419X Category : Medical Languages : en Pages : 301
Book Description
Regulatory T Cells in Health and Disease focuses on the mechanism by which T cells become regulatory T cells, the processes which control the number of regulatory T cells in the blood and tissue, and the ways in which regulatory T cell prevent autoimmune disease and interact with infections and cancer. Contains contributions from leading authorities in the field of regulatory T cell biology Informs and updates on all the latest developments in the field Explores the processes which control the number of regulatory T cells in the blood and tissue, and the ways in which regulatory T cell prevent autoimmune disease and interact with infections and cancer
Author: Stefan de Folter Publisher: Humana Press ISBN: 9781493990412 Category : Science Languages : en Pages : 363
Book Description
This detailed volume provides a collection of protocols for the study of miRNA functions in plants. Beginning with coverage of miRNA function, biogenesis, activity, and evolution in plants, the book continues by guiding readers through methods on the identification and detection of plant miRNAs, bioinformatic analyses, and strategies for functional analyses of miRNAs. Written in the highly 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 laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Plant MicroRNAs: Method and Protocols aims to ensure successful results in the further study of this vital area of plant science.
Author: Publisher: Academic Press ISBN: 9780123969682 Category : Science Languages : en Pages : 0
Book Description
This new volume of Current Topics in Developmental Biology covers developmental timing, with contributions from an international board of authors. The chapters provide a comprehensive set of reviews covering such topics as the timing of developmental programs in Drosophila, temporal patterning of neural progenitors, and environmental modulation of developmental timing.
Author: Jonathan Soboloff Publisher: CRC Press ISBN: 149870509X Category : Medical Languages : en Pages : 258
Book Description
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.
Author: Tilman Borggrefe Publisher: Springer ISBN: 3319895125 Category : Science Languages : en Pages : 417
Book Description
This book describes the Notch signaling pathway with a focus on molecular mechanisms. The Notch signaling pathway is a seemingly simple pathway that does not involve any second messenger. Upon ligand binding two consecutive proteolytic cleavages of the NOTCH receptor release the Notch intracellular domain from the membrane. The Notch intracellular domain migrates into the nucleus and activates gene expression. Recently, new technologies allowed us to better understand this pivotal signaling cascade and revealed new regulatory mechanisms. The different chapters cover many aspects of the Notch signaling focusing on the mechanisms governing the receptor/ligand interaction as well as on the downstream intracellular signaling events. Aspects of both canonical and non-canonical signaling are discussed and the function of Notch signaling in physiological and pathological contexts are elucidated. This book is not only intended for experts but it should also be a useful resource for young, sprouting scientists or interested scientists from other research areas, who may use this book as a stimulating starting point for further discoveries and developments.
Author: Steven Schaffert
Author: Steven Schaffert
Author: Bruce Spiegelman
Author: Jiayi Dong
Author: Ronald Trent
Author: Nik Sheng Ding
Author: 
Author: Stefan de Folter
Author: 
Author: Jonathan Soboloff
Author: Tilman Borggrefe