Role of the IL-23/IL-17 Pathway in Chronic Immune-Mediated Inflammatory Diseases: Mechanisms and Targeted Therapies PDF Download

Author: Elisabetta Bianchi
Publisher: Frontiers Media SA
ISBN: 288971621X
Category : Medical
Languages : en
Pages : 230

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Author: John Y. M. Koo
Publisher: CRC Press
ISBN: 1482215160
Category : Medical
Languages : en
Pages : 422

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Written by experts in the dermatology field, this new fourth edition of Moderate-to-Severe Psoriasis discusses the current use of biologics and other pharmacologic and phototherapy treatments for moderate-to-severe psoriasis. Illustrated with high quality color figures, this standalone text emphasizes safe and effective treatments for the psoriasis patient that are perfect for the dermatologist in daily practice. New to this edition are chapters on day treatment programs, new agents, erythrodermic and pustular psoriasis, special populations, and pharmacogenetics.

Author: Cong-Qiu Chu
Publisher: Springer
ISBN: 3319280406
Category : Medical
Languages : en
Pages : 112

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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.

Author: Valérie Quesniaux
Publisher: Springer Science & Business Media
ISBN: 3764386819
Category : Medical
Languages : en
Pages : 247

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Book Description
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.

Author: Valérie Quesniaux
Publisher: Springer Science & Business Media
ISBN: 3034805225
Category : Medical
Languages : en
Pages : 345

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Book Description
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.

Author: Phoebe Lin
Publisher: Springer Nature
ISBN: 3030228274
Category : Medical
Languages : en
Pages : 208

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Book Description
This unique, comprehensive book provides a much-needed reference on the treatment and management of non-infectious uveitis. Carefully designed, Treatment of Non-infectious Uveitis is the first book of its kind to provide an in-depth, clinically-relevant, expert-driven resource for ophthalmologists focusing on modalities of uveitis treatment, their mechanism of action, dosing, and side effects. Each chapter provides an introduction, mechanism of action, indication, dosage, side effects, and efficacy summaries from clinical trials and other published literature. Topics range from topical treatment, to locally administered therapy including drug-releasing implants, to systemic immunosuppressive treatments both tried and new, as well as surgical management, with each chapter highlighting important practice pearls as well as easy-reference dosing tables, side effects, and lab monitoring pertinent to the agents discussed. The book concludes with a discussion of novel approaches to the treatment of non-infectious uveitis, and special considerations when treating uveitis in the pediatric patient. The majority of patients with non-infectious uveitis are treated by comprehensive ophthalmologists, many of whom are less familiar with established treatment guidelines outlining the role of corticosteroids and immunomodulatory therapy. While the non-specialist, resident, or fellow is sure to benefit from this one-stop guide to uveitis treatment, retina and uveitis specialists alike will also appreciate the practice tips and thorough coverage of this expertly-written reference. Treatment of Non-infectious Uveitis is the ideal reference for all ophthalmologists who seek to improve their understanding of the causes of uveitis and learn how to best treat this condition.

Author: Lingzi Hong
Publisher:
ISBN:
Category : Inflammation
Languages : en
Pages : 177

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Book Description
Interleukin 17 (IL-17, also known as IL-17A) is a key signature cytokine of Th17 cells and is also produced by innate immune cells. While IL-17 is required for host defense against extracellular microorganisms, IL-17 plays a critical role in the pathogenesis of autoimmune and inflammatory diseases, including psoriasis, rheumatoid arthritis, multiple sclerosis, and asthma. IL-17 signals through adaptor protein Act1, resulting in transcription of pro-inflammatory and neutrophil-mobilizing cytokines and chemokines, including CXCL1, TNF, IL-6 and GM-CSF. Mechanisms that degrade inflammatory mRNAs are well known; however, stabilizing mechanisms are poorly understood. We discovered that Act1 also acts as an RNA binding protein to stabilize mRNAs encoding key inflammatory proteins through a stem-loop structure element, named as SBE (SEFIR-binding element). mRNA-bound Act1 directs formation of three compartmentally distinct RNA-protein complexes (RNPs) that regulate three distinct events in inflammatory-mRNA metabolism: preventing mRNA decay in the nucleus, inhibiting mRNA decapping in P bodies and promoting translation. SBE RNA aptamers decreased IL-17-mediated mRNA stabilization in vitro as well as IL-17-induced skin inflammation and airway inflammation in a mouse asthma model, thus providing a therapeutic strategy for autoimmune diseases. These results reveal a network in which Act1 assembles RNPs on the 3' UTRs of select mRNAs and consequently controls receptor-mediated mRNA stabilization and translation during inflammation. Asthma is a T cell-mediated heterogeneous disease clinically characterized by bronchial hyperresponsiveness, inflammation, and airflow obstruction. Glucocorticoids are the gold standard in asthma therapy as they can successfully control asthma in a large proportion. A substantial body of research has shown that interleukin (IL)-17A plays a critical role in the pathogenesis of severe, steroid resistant asthma. Clinical studies have also indicated that a subgroup of asthma patients responded to IL-17 signaling blockers, but the mechanism is not well understood. We showed CEBPB was the critical transcription factor that is synergistically induced by IL17-A and glucocorticoid (GC). In addition, LCN2 and SAA were also synergistically induced by IL17A and glucocorticoid (GC) through CEBPB in cultured airway cells. Mechanistically, IL17A and GC collaboratively regulated CEBPB at both transcriptional and posttranscriptional levels, which involved direct binding and stabilization of CEBPB mRNA by Act1. LCN2 and SAA may serve as LCN2 and SAA as potential circulating biomarkers for endotyping type-17 severe asthma. In one cohort study, severe asthma patients showed significantly higher plasma LCN2 and SAA as compared with healthy controls; a positive correlation was also revealed between blood IL-17A and LCN2 or SAA in patients. Taken together, our study elucidates the molecular mechanism of IL17A-Act1/CEBPB axis on steroid-resistant IL17-A targets, LCN2 and SAAs, which may serve as useful biomarkers to distinguish type-17 severe asthma endotype for anti-IL17A therapy.

Author: Kazuwa Nakao
Publisher: Springer
ISBN: 4431556516
Category : Science
Languages : en
Pages : 330

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Book Description
This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.

Author: Valérie Quesniaux
Publisher: Birkhäuser
ISBN: 9783764394950
Category : Medical
Languages : en
Pages : 244

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Book Description
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.

Author: Sharlene Velichko
Publisher:
ISBN: 9781124908731
Category :
Languages : en
Pages :

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Book Description
The role of the proinflammatory cytokine interleukin-17 (IL-17) in the airway has been under investigation for the last 12 years. Many studies have been published demonstrating its pleiotropic role in the production of chemokines, cytokines, mucins, and antimicrobial proteins. Many in vivo models have demonstrated the association of IL-17 in airway inflammation in response to allergens as well as environmental insults, as well as chronic inflammatory lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease and asthma. However, relatively little is known regarding the downstream signaling mechanisms by which IL-17 mediates its many effects. What is known is that the signaling is complex; IL-17 has been shown to involve multiple signaling pathways, including: the canonical NF-kappaB pathway, multiple mitogen-activated protein (MAP) kinase pathways, as well as C/EBP, PI-3 kinase and JAK. Both cell type and target gene appear to determine the signaling pathway involved downstream of IL-17. Little is known regarding the protein-protein interactions that mediate these signaling events. What is known is that the intracellular protein Act1 (also known as CIKS) is an important downstream mediator of IL-17 induced signaling. Cells derived from Act1-deficient mice are largely unresponsive to IL-17A stimulation. Act1 has been shown to contain both TRAF6 and IL-17 receptor binding sites, and therefore acts as an intermediate to connect the activated IL-17 receptor complex to pathways downstream of TRAF6. However, Act1 has additional functions as well. It can also bind to the IL-25, CD40 and BAFF-R receptors, and has recently been shown to act as a U-box type E3 ubiquitin ligase. Recently, a single nucleotide polymorphism (SNP) that encodes a loss-of-function mutation in the gene for Act1, TRAF3IP2, was associated with psoriasis, an autoimmune inflammatory skin disease, and psoriatic arthritis. As IL-17 is associated with the pathogenesis of psoriasis, this is counter-intuitive to the known functions of Act1, indicating that Act1 may have other functions as well. This dissertation details a novel nuclear function for Act1 as a transcriptional enhancer. Subsequent RNA-seq comparison of cells ectopically expressing Act1 and IL-17A stimulated cells identified a number of cornified envelope constituents whose expression is up-regulated by both Act1 and IL-17. The cornified envelope is a structure formed in the outermost layer of stratified squamous epithelia. Finally, we detail the use of a yeast two hybrid assay to identify novel Act1 interacting proteins, and further characterize the interaction of Act1 with one of these proteins, COMMD1 (copper metabolism (Murr1) domain containing 1), which might represent a new target of Act1's ubiquitin ligase activity.