Th 17 Cells Role In Inflammation And Autoimmune Disease

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.

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.

The knowledge of Th17 cells and other cell populations which secrete IL-17A, and/or IL-22 has expanded tremendously since the publication of the first edition “Th17 Cells: Role in Inflammation and Autoimmune Disease” in 2008. The present volume has been completely revised with the addition of new chapters on the IL-17 receptor family and signaling, and an in-depth review of IL-22 and innate lymphoid cells. The differentiation of naïve T cells into regulatory T cells and Th17 cells as well as the plasticity of Th17 cells is discussed. The role of IL-22 in cutaneous inflammation including psoriasis has been reviewed. In addition, the volume contains critical updates on autoimmunity, organ transplantation, tumor immunology and genetic mouse models for mechanistic studies. Lastly, the latest clinical progress in neutralizing antibodies to IL-17A, IL-17RA not only confirms the therapeutic promise foreseen in 2008, but also improves our knowledge of the pathogenesis of autoimmune diseases. In summary, this is a timely update and important review of the clinical and experimental aspects of IL-17, IL-22 and their producing cells.

“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 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

This book provides an overview of the discovery and structure of IL-17, including its pathogenesis and role in chronic inflammation and autoimmunity. To capture the latest developments and product approvals the book also discusses the therapeutic advances and looks at emerging therapies targeting the IL-17 pathway. IL-17 is a pro-inflammatory cytokine that has a key role in inflammation, autoimmunity, and host defense in a number of inflammatory disorders such as rheumatoid arthritis, psoriatic arthritis and psoriasis, ankylosing spondylitis, multiple sclerosis, and inflammatory bowel disease. The discovery of the IL-17-Th17 pathway has seen exciting development in the field of immunology and inflammation research, which has led to a number of recent regulatory approvals.