Progress in Inflammation Research – serie

Perinatal psychiatry is an emerging field that investigates the role of perinatal events – for example pregnancy complications and infections – in the development of neuropsychiatric conditions, such as schizophrenia and mood disorders. Among the implicated pathological mechanisms, perinatal-induced inflammation seems to play a major role and is being considered as a potential target for therapeutic intervention.  Bringing together various approaches in the field (preclinical and clinical, epidemiological, immunological and genetic methods), the book discusses the available evidence, the putative mechanisms and the challenges ahead.

Perinatal psychiatry is an emerging field that investigates the role of perinatal events – for example pregnancy complications and infections – in the development of neuropsychiatric conditions, such as schizophrenia and mood disorders. Among the implicated pathological mechanisms, perinatal-induced inflammation seems to play a major role and is being considered as a potential target for therapeutic intervention.  Bringing together various approaches in the field (preclinical and clinical, epidemiological, immunological and genetic methods), the book discusses the available evidence, the putative mechanisms and the challenges ahead.

Nrf2, a transcription factor that mediates transcriptional responses to oxidative and xenobiotic stresses, plays a central role in cellular protection against internal or external toxins. Defects in Nrf2 and the relevant regulatory pathways are associated with a number of pathologies including inflammation, respiratory diseases, cardiovascular dysfunctions, metabolic syndrome and diabetes, neurodegeneration, and cancer. This book comprehensively reviews the up-to-date discoveries for the roles of Nrf2 in several human diseases in the context of inflammation. In particular, the molecular mechanisms that mediate the functions of Nrf2 and its interacting network in inflammation and pathogenesis are explicated. In addition, the research and therapeutic applications of Nrf2-targeting compounds in different diseases were summarized. This book is expected to be a valuable reference for worldwide researchers conducting both mechanistic and therapeutic studies of Nrf2 and relevant factors.

Macrophages are core components of the innate immune system. Once activated, they may have either pro- or anti-inflammatory effects that include pathogen killing, safe disposal of apoptotic cells or tissue renewal. The activation state of macrophages is conceptualized by the so-called M1/M2 model of polarization. M2 macrophages are not simply antagonists of M1 macrophages; rather, they represent a network of tissue resident macrophages with roles in tissue development and organ homeostasis. M2 macrophages govern functions at the interfaces of immunity, tissue development and turnover, metabolism, and endocrine signaling. Dysfunction in M2 macrophages can ruin the healthy interplay between the immune system and metabolic processes, and lead to diseases such as insulin resistance, metabolic syndrome, and type 1 and 2 diabetes mellitus. Furthermore, M2 macrophages are essential for healthy tissue development and immunological self-tolerance. Worryingly, these functions of M2 macrophages can also be disrupted, resulting in tumor growth and autoimmunity. This book comprehensively discusses the biology of M2 macrophages, summarizes the current state of knowledge, and highlights key questions that remain unanswered.

Macrophages are core components of the innate immune system. Once activated, they may have either pro- or anti-inflammatory effects that include pathogen killing, safe disposal of apoptotic cells or tissue renewal. The activation state of macrophages is conceptualized by the so-called M1/M2 model of polarization. M2 macrophages are not simply antagonists of M1 macrophages; rather, they represent a network of tissue resident macrophages with roles in tissue development and organ homeostasis. M2 macrophages govern functions at the interfaces of immunity, tissue development and turnover, metabolism, and endocrine signaling. Dysfunction in M2 macrophages can ruin the healthy interplay between the immune system and metabolic processes, and lead to diseases such as insulin resistance, metabolic syndrome, and type 1 and 2 diabetes mellitus. Furthermore, M2 macrophages are essential for healthy tissue development and immunological self-tolerance. Worryingly, these functions of M2 macrophages can also be disrupted, resulting in tumor growth and autoimmunity. This book comprehensively discusses the biology of M2 macrophages, summarizes the current state of knowledge, and highlights key questions that remain unanswered.

TLR4 is one of the most important innate immunity receptors, its function mainly consisting in the activation of inflammatory pathways in response to stimulation by Pathogen-Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Pattern molecules (DAMPs).This volume critically reviews the different types of TLR4 activators and inhibitors, discusses the role of molecular aggregates in agonism/antagonism as well as the pivotal role of the CD14 receptor in the modulation of TLR4 signal and the molecular details and actors of the intracellular cascade.The book presents the role of TLR4 in several pathologies, such as sepsis and septic shock caused by receptor activation by gram-negative bacterial lipopolysaccharide (LPS), in neurodegenerative and neurological diseases such as Parkinson and Alzheimer’s diseases,  and Amyotrophic Lateral Sclerosis (ALS). It reviews the role of TLR4 in neural stem cell-mediated neurogenesis andneuroinflammation and in Human Induced Pluripotent Stem Cells and Cerebral Organoids and discusses the emerging role of micro-RNA (miRNA) regulation by TLR4.

TLR4 is one of the most important innate immunity receptors, its function mainly consisting in the activation of inflammatory pathways in response to stimulation by Pathogen-Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Pattern molecules (DAMPs).This volume critically reviews the different types of TLR4 activators and inhibitors, discusses the role of molecular aggregates in agonism/antagonism as well as the pivotal role of the CD14 receptor in the modulation of TLR4 signal and the molecular details and actors of the intracellular cascade.The book presents the role of TLR4 in several pathologies, such as sepsis and septic shock caused by receptor activation by gram-negative bacterial lipopolysaccharide (LPS), in neurodegenerative and neurological diseases such as Parkinson and Alzheimer’s diseases,  and Amyotrophic Lateral Sclerosis (ALS). It reviews the role of TLR4 in neural stem cell-mediated neurogenesis andneuroinflammation and in Human Induced Pluripotent Stem Cells and Cerebral Organoids and discusses the emerging role of micro-RNA (miRNA) regulation by TLR4.

This book provides comprehensive information, both for clinicians and scientists, on the basic mechanisms, clinical features, and therapeutic approaches to epilepsy as an inflammatory disease. Inflammation has been for many years considered as an etiologic player (and a therapeutic target) for a specific group of epilepsies. However, it turns out that this concept underestimated the impact of inflammation in seizure disorders. Many accepted therapies for non-inflammatory epilepsies act in part as an inflammatory drug. The CNS actively responds to acute immune challenges by altering body temperature, stimulating the HPA axis, as well as up- and down-regulating specific sympathetic pathways.

This book provides comprehensive information, both for clinicians and scientists, on the basic mechanisms, clinical features, and therapeutic approaches to epilepsy as an inflammatory disease. Inflammation has been for many years considered as an etiologic player (and a therapeutic target) for a specific group of epilepsies. However, it turns out that this concept underestimated the impact of inflammation in seizure disorders. Many accepted therapies for non-inflammatory epilepsies act in part as an inflammatory drug. The CNS actively responds to acute immune challenges by altering body temperature, stimulating the HPA axis, as well as up- and down-regulating specific sympathetic pathways.

This edited collection of 12 chapters by research workers from a wide range of disciplines resolves the confusion that currently surrounds the “hygiene hypothesis” by considering the human need for exposure to microorganisms from an evolutionary point of view.  The book explains why we evolved a requirement for exposure to microbiota from our mothers, from other people, and from the natural environment. It also explains the physiological roles of these exposures, what goes wrong when the exposures are distorted and how human lifestyles and activities, including degradation of the natural environment, are leading to this distortion.  Particular attention is given to the range of pathologies associated with inappropriate microbial exposures and inappropriate colonization, including immunoregulatory problems such as allergies and autoimmunity, metabolic problems such as obesity and diabetes, and problems of central nervous system function and neurodegeneration.  This book is of profound relevance to most medical disciplines, but also to those concerned with preserving the natural environment and with developing healthier urbanisation.

This edited collection of 12 chapters by research workers from a wide range of disciplines resolves the confusion that currently surrounds the “hygiene hypothesis” by considering the human need for exposure to microorganisms from an evolutionary point of view.  The book explains why we evolved a requirement for exposure to microbiota from our mothers, from other people, and from the natural environment. It also explains the physiological roles of these exposures, what goes wrong when the exposures are distorted and how human lifestyles and activities, including degradation of the natural environment, are leading to this distortion.  Particular attention is given to the range of pathologies associated with inappropriate microbial exposures and inappropriate colonization, including immunoregulatory problems such as allergies and autoimmunity, metabolic problems such as obesity and diabetes, and problems of central nervous system function and neurodegeneration.  This book is of profound relevance to most medical disciplines, but also to those concerned with preserving the natural environment and with developing healthier urbanisation.

The volume summarizes the most recent advances in our understanding of the mesentery and explains the how these are important in inflammation.  It comprises a series of state of the art chapters by leading authorities in each area.  It explains how recent advances in our understanding of the mesenteric organ, have advanced the diagnosis and treatment abdominal and systemic conditions including cancer, inflammatory bowel disease and endocrine conditions such as diabetes, and circulatory disorders such as atherosclerosis.

The volume summarizes the most recent advances in our understanding of the mesentery and explains the how these are important in inflammation.  It comprises a series of state of the art chapters by leading authorities in each area.  It explains how recent advances in our understanding of the mesenteric organ, have advanced the diagnosis and treatment abdominal and systemic conditions including cancer, inflammatory bowel disease and endocrine conditions such as diabetes, and circulatory disorders such as atherosclerosis.

Imaging Inflammation provides updates on cutting-edge imaging methods being applied to problems in inflammation research. From state-of-the-art research tools to diagnostic tests, and from single-cell to whole-body imaging, this volume offers a comprehensive overview of how imaging experts across a range of disciplines are expanding our understanding of inflammation and immunity.

Imaging Inflammation provides updates on cutting-edge imaging methods being applied to problems in inflammation research. From state-of-the-art research tools to diagnostic tests, and from single-cell to whole-body imaging, this volume offers a comprehensive overview of how imaging experts across a range of disciplines are expanding our understanding of inflammation and immunity.

For over 50 years, clinicians have known that macrolide antibiotics have effects on inflammation and the immune system that are not related to their antimicrobial properties. These immunomodulatory properties, best described for treating inflammatory airway diseases, protect the lung and the host and improve clinical status. This book summarizes our current knowledge regarding proposed mechanisms for these properties, established clinical results, and what the future may hold with emphasis on novel clinical applications and the fascinating development of non-antimicrobial macrolides with preserved and enhanced immunomodulatory properties.

For over 50 years, clinicians have known that macrolide antibiotics have effects on inflammation and the immune system that are not related to their antimicrobial properties. These immunomodulatory properties, best described for treating inflammatory airway diseases, protect the lung and the host and improve clinical status. This book summarizes our current knowledge regarding proposed mechanisms for these properties, established clinical results, and what the future may hold with emphasis on novel clinical applications and the fascinating development of non-antimicrobial macrolides with preserved and enhanced immunomodulatory properties.

The circadian clock is a complex cellular mechanism that controls numerous key physiological processes and maintains cellular, tissue, and systemic homeostasis. Disruption of the clock system influences the immune response and brain functions. Immune activation is closely linked with inflammation, neurodegeneration, aging, and other peripheral and central nervous system-related abnormalities. There is increasing evidence that cellular inflammation affects sleep and circadian rhythms and vice-versa. This book offers a structured overview that focuses on the multi-angle interaction of circadian rhythms, sleep, and inflammatory response in normal or pathological conditions.

The circadian clock is a complex cellular mechanism that controls numerous key physiological processes and maintains cellular, tissue, and systemic homeostasis. Disruption of the clock system influences the immune response and brain functions. Immune activation is closely linked with inflammation, neurodegeneration, aging, and other peripheral and central nervous system-related abnormalities. There is increasing evidence that cellular inflammation affects sleep and circadian rhythms and vice-versa. This book offers a structured overview that focuses on the multi-angle interaction of circadian rhythms, sleep, and inflammatory response in normal or pathological conditions.

The inflammasome was first described in 2002 as a molecular complex activating proinflammatory caspases and therefore regulating the maturation and biological activities of cytokines such as IL-1 and IL-18. This finding was substantiated by the identification of several mutations in the cias1 gene, encoding the human NLRP3 protein, responsible for several autoinflammatory disorders such as the Muckle Wells syndrome. Since, the interest for this complex has constantly increased and several inflammasome complexes with different specificities have been described. These inflammasomes sense a wide variety of pathogens and danger signals and are key players in the inflammatory response. With the contributions of leading international experts in the field, this book provides an extensive overview of the current knowledge of inflammasome biology and their role in health and disease.

Proteases are everywhere from prokaryotes to eukaryotes, from virus to bacteria and in all human tissues, playing a role in many biological functions. Among these functions, the inflammatory reaction is of particular interest.  In inflamed tissues, proteases can have a microbial and/or host origin and are involved not only in tissue remodeling, but also in specific signaling to resident or inflammatory cells, thereby contributing to the innate immune response.This volume presents all advances in our knowledge of the role proteases and their inhibitors play in various diseases associated with inflammatory response. Mechanisms involved in protease signaling to cells are presented, and the different types of proteases that are present at inflammatory sites and their effects on the course of inflammation are discussed. Finally, the evidence for considering proteases and their receptors as potential molecular targets for therapeutic interventions in the treatment of inflammatory diseases is discussed in the context of specific organ inflammatory pathologies (the lung, gastrointestinal tract, skin, joints, etc.).

Proteases are everywhere from prokaryotes to eukaryotes, from virus to bacteria and in all human tissues, playing a role in many biological functions. Among these functions, the inflammatory reaction is of particular interest.  In inflamed tissues, proteases can have a microbial and/or host origin and are involved not only in tissue remodeling, but also in specific signaling to resident or inflammatory cells, thereby contributing to the innate immune response.This volume presents all advances in our knowledge of the role proteases and their inhibitors play in various diseases associated with inflammatory response. Mechanisms involved in protease signaling to cells are presented, and the different types of proteases that are present at inflammatory sites and their effects on the course of inflammation are discussed. Finally, the evidence for considering proteases and their receptors as potential molecular targets for therapeutic interventions in the treatment of inflammatory diseases is discussed in the context of specific organ inflammatory pathologies (the lung, gastrointestinal tract, skin, joints, etc.).

The inflammasome was first described in 2002 as a molecular complex activating proinflammatory caspases and therefore regulating the maturation and biological activities of cytokines such as IL-1 and IL-18. This finding was substantiated by the identification of several mutations in the cias1 gene, encoding the human NLRP3 protein, responsible for several autoinflammatory disorders such as the Muckle Wells syndrome. Since, the interest for this complex has constantly increased and several inflammasome complexes with different specificities have been described. These inflammasomes sense a wide variety of pathogens and danger signals and are key players in the inflammatory response. With the contributions of leading international experts in the field, this book provides an extensive overview of the current knowledge of inflammasome biology and their role in health and disease.

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.

Antimicrobial peptides have been the subject of intense research in the past decades, and are now considered as an essential part of the defense system in bacteria, plants, animals and humans. his book provides an update on these effector molecules of the innate immune system both for researchers who are already actively involved in the area, and for those with a general interest in the topic. The book starts with an overview of the evolution of cysteine-containing antimicrobial peptides (including defensins), and the role of these peptides in host defense in plants and micro-organisms. The realization that antimicrobial peptides also display functions distinct from their direct antimicrobial action is the focus of the next chapters, and puts these peptides center stage in immunity and wound repair.  Further chapters discuss the role of antimicrobial peptides in disease, by providing an overview of mechanisms in bacterial resistance to antimicrobial peptides and a discussion of their role in inflammatory bowel disease, cystic fibrosis lung disease and chronic obstructive pulmonary disease. Finally, the book shows how knowledge of the function of antimicrobial peptides and their regulation can be used to design new therapies for inflammatory and infectious disorders. This is a very important area of research because of the increase in resistance of micro-organisms to conventional antibiotics. Therefore the use of synthetic or recombinant peptides, or agents that stimulate the endogenous production of antimicrobial peptides, provides an attractive alternative for conventional antibiotics.

Antimicrobial peptides have been the subject of intense research in the past decades, and are now considered as an essential part of the defense system in bacteria, plants, animals and humans. his book provides an update on these effector molecules of the innate immune system both for researchers who are already actively involved in the area, and for those with a general interest in the topic. The book starts with an overview of the evolution of cysteine-containing antimicrobial peptides (including defensins), and the role of these peptides in host defense in plants and micro-organisms. The realization that antimicrobial peptides also display functions distinct from their direct antimicrobial action is the focus of the next chapters, and puts these peptides center stage in immunity and wound repair.  Further chapters discuss the role of antimicrobial peptides in disease, by providing an overview of mechanisms in bacterial resistance to antimicrobial peptides and a discussion of their role in inflammatory bowel disease, cystic fibrosis lung disease and chronic obstructive pulmonary disease. Finally, the book shows how knowledge of the function of antimicrobial peptides and their regulation can be used to design new therapies for inflammatory and infectious disorders. This is a very important area of research because of the increase in resistance of micro-organisms to conventional antibiotics. Therefore the use of synthetic or recombinant peptides, or agents that stimulate the endogenous production of antimicrobial peptides, provides an attractive alternative for conventional antibiotics.

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.

Heat shock proteins (HSP) have received ample interest by immunologists over recent years. Initially they were found to be dominantly immunogenic microbial antigens. The connection with inflammation was established when it was uncovered that T cells specific for these antigens have a crucial role in the induction and regulation of experimental arthritis. Since then, the raised presence of immunity to HSPs in virtually all conditions of inflammation, including autoimmune diseases, transplant rejection and atherosclerosis, has emphasised the critical significance of immunity to HSPs in inflammatory diseases.

Several new developments in the field of neuroimmunology with focus on the brain-to-immune system communication have been the incentive for this PIR volume. It covers topics such as brain-immune interactions, the impact of stress on the immune response, pain and immunosuppression, the modulation of inflammation and pain by the sympathetic nervous system, consequences of nerve injury for the immune system, neuronal mechanisms of immune cell recruitment, and the modulation of the immune response by corticotropin-releasing hormone or adenosine. The authors are a unique group of scientists who are all interested in brain-to-immune interactions; however, each from a different perspective. The volume will serve both neurobiologists and immunologists to understand the influence of the central nervous system on peripheral inflammation. Many aspects of this book will also be stimulating for researchers in the pain field.