Th17 Cells In Health And Disease

“About 25 years ago, Mosmann & Coffman introduced the TH1 / TH2 paradigm of T helper cell differentiation which helped explain many aspects of adaptive immunity from eliminating intracellular versus extracellular pathogens to induction of different types of tissue inflammation. However, TH1 / TH2 paradigm could not adequately explain development of certain inflammatory responses which provided impetus for the discovery of a new subset of T cells called TH17 cells. After the discovery of differentiation and transcription factors for TH17 cells, it was clear that TH17 cells represent an independent subset of T cells with specific functions in eliminating certain extracellular pathogens, presumably not adequately handled by TH1 or TH2 cells. The major role of TH17 cells has been described in inducing auto-immune tissue inflammation. The discovery of TH17 cells has expanded the TH1 / TH2 paradigm, and the integration of TH17 cells with TH1 and TH2 effector T cells is beginning to explain the underlying mechanisms of tissue inflammation in a number of infections and auto-immune disease settings.” - From Chapter One by Vijay K. Kuchroo, Harvard University, USA “The recently identified Interleukin 17 (IL-17) cytokine family contributes to immunity to infectious diseases and chronic inflammatory diseases. Further studies on the regulation and function of this important cytokine family may provide better understanding on the roles of the IL-17 family in immune-mediated diseases; such knowledge may lead to the development of immunotherapeutic strategies for treatment of several inflammatory diseases.” - From Chapter Two by Chen Dong, University of Texas and MD Anderson Cancer Center, USA

“About 25 years ago, Mosmann & Coffman introduced the TH1 / TH2 paradigm of T helper cell differentiation which helped explain many aspects of adaptive immunity from eliminating intracellular versus extracellular pathogens to induction of different types of tissue inflammation. However, TH1 / TH2 paradigm could not adequately explain development of certain inflammatory responses which provided impetus for the discovery of a new subset of T cells called TH17 cells. After the discovery of differentiation and transcription factors for TH17 cells, it was clear that TH17 cells represent an independent subset of T cells with specific functions in eliminating certain extracellular pathogens, presumably not adequately handled by TH1 or TH2 cells. The major role of TH17 cells has been described in inducing auto-immune tissue inflammation. The discovery of TH17 cells has expanded the TH1 / TH2 paradigm, and the integration of TH17 cells with TH1 and TH2 effector T cells is beginning to explain the underlying mechanisms of tissue inflammation in a number of infections and auto-immune disease settings.” - From Chapter One by Vijay K. Kuchroo, Harvard University, USA “The recently identified Interleukin 17 (IL-17) cytokine family contributes to immunity to infectious diseases and chronic inflammatory diseases. Further studies on the regulation and function of this important cytokine family may provide better understanding on the roles of the IL-17 family in immune-mediated diseases; such knowledge may lead to the development of immunotherapeutic strategies for treatment of several inflammatory diseases.” - From Chapter Two by Chen Dong, University of Texas and MD Anderson Cancer Center, USA

The IL-17 cytokines represent a novel family of cytokines, which defines a new effector T cell, the Th17 cell, and extend the Th1-Th2 paradigm. Th17 cells in part co-express at least IL-17A and IL-17F, IL-21 and IL-22. IL-17 A/F are produced by T cells ( and ), iNKT cells, and possibly neutrophils, dendritic cells and Paneth cells. The regulation of IL-17 family member’s expression, and the identification of effector mechanisms are an area of intense current research. Recognized regulators of IL-17A expression include the nuclear receptor ROR t, proinflammatory cyt- ines such as IL-1, IL-6 with TGF- , IL-21, IL-23 IL-25 in the absence of IFN- and IL-4, which are discussed. Recent data suggest that IL-17A may have a dual fu- tion – pro-inflammatory and anti-inflammatory- suggesting that IL-17A may also contribute to terminate inflammation. Further, a reciprocal regulation of Th17 and regulatory T cells including the role of retinoic acid and TGF- is discussed. The discovery that patients with rheumatoid arthritis, allergic disorders, psor- sis and inflammatory bowel disease express IL-17A generated interest in the medical community and instigated a flurry of experimental research on the potential role of Th17 in inflammatory diseases. Experimental studies confirmed that IL-17A is induced and is critical for the development of allergic lung inflammation, arthritis, bacterial sepsis, experimental allergic encephalomyelitis and myocarditis, as well as other inflammatory con- tions including organ transplantation. The role of IL-17F and IL-22 is still poorly defined and is only slowly emerging.

A translational overview of neuroimmune diseases for neuroscientists and clinicians that clarifies the pathological mechanisms underlying neuroimmune diseases and builds a comprehensive bridge between the latest research findings and their clinical implications in daily practice. The material is presented in two steps. The first section comprises a review of the pathogenic actions of immune cells in brain diseases. Here the authors discuss the mechanisms through which immune cells disrupt the functions of nerve cells. The second section explores the ways in which the brain becomes dysfunctional due to impaired nerve cell function. Based on pathogenesis, diagnostic and therapeutic strategies are discussed for each clinical category. The book will be invaluable for use in clinical practice of neuroimmune diseases

This book guides the reader through the latest research on the cytokine network, covering signaling pathways, control of the immune response, and potential therapeutics. Different cytokines stimulate diverse responses in various phases of inflammation and immunity, including the innate immune response, the generation of effector T cells, and the development of antibodies by the humoral immune system. It is now clear that the pathophysiology of many infectious, autoimmune, allergic, and malignant diseases can be largely explained by which cytokines are induced and subsequently regulate the cellular responses. In clinical medicine, cytokines are involved in a wide spectrum of diseases. This book describes in three parts the properties and roles of 15 key cytokines under physiological and pathological conditions. Part I presents nine cytokines associated with inflammatory disorders, pro-inflammatory cytokines, and the recently identified new helper T (Th) subset: Th17 cells. Part II gives details of three cytokines associated with allergic disorders, including Th2 responses and recently identified types of innate cells. Part III describes three cytokines that are associated with immunological tolerance and anti-inflammation, including regulatory T (Treg) cells, IL-10-producing Treg (Tr1) cells, and inducible IL-35-producing Treg (iTr35) cells. Cytokines are considered to be important as therapeutic targets for specific agonists or antagonists in numerous immune and inflammatory diseases. The ultimate goal of this book is to facilitate the development of therapeutic treatments for such diseases which has been limited by an insufficient understanding of the biology of cytokines and the complicated network that they create.

Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation: Models in Discovery and Translation, Second Edition once again provides clinical and scientific researchers with a deep understanding of the current research in this field and the implications for translational practice. By providing an overview of the immune biology of HSCT, an explanation of immune rejection, and detail on antigens and their role in HSCT success, this book embraces biologists and clinicians who need a broad view of the deeply complex processes involved. It then moves on to discuss the immunobiology mechanisms that influence graft-versus-host disease (GVHD), graft-versus-leukemia effect, and transplantation success. Using illustrative figures, highlighting key issues, describing recent successes, and discussing unanswered questions, this book sums up the current state of HSCT to enhance the prospects for the future. The second edition is fully revised and includes new chapters on microbiome, metabolism, kinase targets, micro-RNA and mRNA regulatory mechanisms, signaling pathways in GVHD, innate lymphoid system development, recovery and function in GVHD, genetically engineered T-cell therapies, immune system engagers for GVHD and graft-versus-tumor, and hematopoietic cell transplant for tolerance induction in solid organ grafts. Brings together perspectives from leading laboratories and clinical research groups to highlight advances from bench to the bedside Guides readers through the caveats that must be considered when drawing conclusions from studies with animal models before correlating to clinical allogeneic hematopoietic stem cell transplantation (HSCT) scenarios Categorizes the published advances in various aspects of immune biology of allogeneic HSCT to illustrate opportunities for clinical applications

“Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists...). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.

The Mosaic of Autoimmunity: The Novel Factors of Autoimmune Diseases describes the multifactorial origin and diversity of expression of autoimmune diseases in humans. The term implies that different combinations of factors in autoimmunity produce varying and unique clinical pictures in a wide spectrum of autoimmune diseases. Most of the factors involved in autoimmunity can be categorized into four groups: genetic, immune defects, hormonal and environmental factors. In this book, the environmental factors are reviewed, including infectious agents, vaccines as triggers of autoimmunity, smoking and its relationship with rheumatoid arthritis, systemic lupus erythematosus, thyroid disease, multiple sclerosis and inflammatory bowel diseases. An entirely new syndrome, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA), is also included, along with other diseases that are now recognized as having an autoimmune etiopathogenesis. Highlights the concept of the mosaic of autoimmune manifestations Includes new visions on unsuspected molecules Provides updated knowledge to physicians helping patients with autoimmune diseases Presents thorough, up-to-date information on specific diseases, along with clinical applications