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Regulation of Inflammation; Its Resolution and Therapeutic Targeting

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453597 Year: Pages: 105 DOI: 10.3389/978-2-88945-359-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-02-27 16:16:45
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Inflammation is a fundamental protective mechanism and at the same time the driving force of a variety of major diseases in humans. Indeed, acute self-resolving inflammation usually plays a positive role for the host, as exemplified by infectious diseases where its positive role is well established and testified by its perception as innate immunity. On the other hand, non-resolving inflammation and consequent chronicization is a key determinant of immunopathology and clinical manifestations of most major diseases in humans. As a consequence, it is increasing appreciated that the problem with inflammation is not how often it starts, but how often it fails to resolve. Appropriate resolution of inflammatory responses, which also drives activation of tissue damage repair mechanisms and return of local tissues to homeostasis, is a necessary process for ongoing health. Interestingly, cells sustaining these processes are also key to the proinflammatory responses, and the underlying “pro-resolving” molecular pathways are triggered as part of the pro-inflammatory response. This clearly indicates resolution of inflammation as an active process requiring functional repolarization of inflammatory cells that calls our attention on the underlying molecular mechanisms. The increasing number of anti-inflammatory drugs best-sellers in the pharma market is a clear indication of the relevance of having inflammation under check; nonetheless, there is still a great need for better acting pharmacological tools for the control of inflammation. Indeed, the remarkable success of biological drugs targeting proinflammatory cytokines has indicates that tools able to block proinflammatory mediators have promising applications, but at the same time has made clear that there are intrinsic limitations to this approach which frequently vanish undermine the activity of single targeting drugs, including the well-known redundancy of inflammatory mediators. Under self-limiting conditions inflammation spontaneously resolves in an active process. Some cellular and molecular mechanisms involved in inflammation resolution have been uncovered in the recent past, and include generation of specific cytokines, apoptosis of inflammatory leukocytes, lipid mediators, macrophage repolarization and others are likely to be revealed in the next future, since loss-of-function mutations of an increasing number of genes results in the development of spontaneous inflammation in experimental animals. We argue that “pushing for“ inflammation resolution by exploiting active naturally-occurring pro-resolving processes may have significant advantages over the attempt to simply “push back” inflammation by passive blockade of proinflammatory mediators. At present the research in the field of inflammation aims at identifying and validates new molecules involved in the resolution of inflammation as a basis for the development of innovative therapeutic strategies in chronic inflammatory and autoimmune diseases. This involves the discovery of new natural or synthetic “pro-resolving” molecules from plant and animals and the investigation of endogenous inflammation “pro-resolving” mechanisms, including atypical chemokine receptors, decoy receptors, and microRNA. An extensive effort is focused on the regulation by “pro-resolving” agents on two molecular systems of key relevance in inflammation: the chemokine system, which regulates recruitment, permanence and egress of leukocyte in tissues; and the Toll Like Receptor (TLR)/IL-1R system, which is central for the activation of infiltrating leukocytes.

Microglia in Health and Disease: A Unique Immune Cell Population

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889456017 Year: Pages: 108 DOI: 10.3389/978-2-88945-601-7 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology --- Allergy and Immunology
Added to DOAB on : 2019-01-23 14:53:43
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Microglia are essential for the development and function of the adult brain. Their ontogeny, together with the absence of turnover from the periphery and the singular environment of the central nervous system (CNS), make microglia a unique cell population compared to other tissue-macrophages. The unique properties and functions of microglial cells, such as their role in synaptic pruning or the exceptional capacity to scan the brain parenchyma and rapidly react to its perturbations, have emerged in recent years. In the coming years, understanding how microglia acquire and maintain their unique profiles in order to fulfil distinct tasks in the healthy CNS and how these are altered in disease, will be essential to develop strategies to diagnose or treat CNS disorders with an immunological component.This Research Topic covers several aspects of microglial biology, ranging from their origin and the functional role of microglia during development and lifespan, their molecular properties compared with other brain and peripheral immune cells to microglial phenotypes and functional states in neurodegenerative diseases and brain tumours. In conclusion, the present Research Topic provides a comprehensive overview of our current understanding of several cellular and molecular mechanisms that make microglia a unique immune cell population within the healthy CNS as well as under inflammatory, neurodegenerative and tumorigenic processes.

Neuro-Immune Interactions in Inflammation and Autoimmunity

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455331 Year: Pages: 222 DOI: 10.3389/978-2-88945-533-1 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2019-01-23 14:53:42
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The nervous system plays an important role in the regulation of immunity and inflammation. On the other hand unbalanced immune responses in inflammatory and autoimmune conditions may have a deleterious impact on neuronal integrity and brain function.Recent studies have characterized neural pathways communicating peripheral inflammatory signals to the CNS, and brain- and spinal cord-derived circuitries controlling various innate and adaptive immune responses and inflammation. A prototypical neural reflex circuit that regulates immunity and inflammation is the vagus nerve-based “inflammatory reflex”. Ongoing research has revealed cellular and molecular mechanisms underlying these neural circuits and indicated new therapeutic approaches in inflammatory and autoimmune disorders. Pharmacological and bioelectronic modulation of neural circuitry has been successfully explored in preclinical settings of sepsis, arthritis, inflammatory bowel disease, obesity-driven disorders, diabetes and other diseases. These studies paved the way to successful clinical trials with bioelectronic neuronal modulation in rheumatoid arthritis and inflammatory bowel disease.Dysregulated release of cytokines and other inflammatory molecules may have a severe impact on brain function. Brain inflammation (neuroinflammation), imbalances in brain neuronal integrity and neurotransmitter systems, and cognitive impairment are characteristic features of post-operative conditions, sepsis, liver diseases, diabetes and other disorders characterized by immune and metabolic dysregulation. Derangements in cytokine release also play a pivotal role in depression. Characteristic brain reactive antibodies in autoimmune conditions, including systemic lupus erythematosus and neuromyelitis optica, significantly contribute to brain pathology and cognitive impairment. These studies, and the simultaneous characterization of neuro-protective cytokines, identified new therapeutic approaches for treating neurological complications in inflammatory and autoimmune disorders.This Frontiers Research Topic is a forum for publishing research findings and methodological and conceptual advances at the intersection of immunology and neuroscience. We hope that presenting new insight into bi-directional neuro-immune communication in inflammation and autoimmunity will foster further collaborations and facilitate the development of new efficient therapeutic strategies.

Immunobiotics: Interactions of Beneficial Microbes with the Immune System

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453825 Year: Pages: 309 DOI: 10.3389/978-2-88945-382-5 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology --- Science (General) --- Microbiology
Added to DOAB on : 2018-11-16 17:17:57
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The term “immunobiotics” has been proposed to define microbial strains able to beneficially regulate the mucosal immune system. Research in immunobiotics has significantly evolved as researchers employed cutting-edge technologies to investigate the complex interactions of these beneficial microorganisms with the immune system. During the last decade, our understanding of immunobiotics-host interaction was profoundly transformed by the discovery of microbial molecules and host receptors involved in the modulation of gut associated immune system, as well as the systemic and distant mucosal immune systems. In recent years, there has been a substantial increase in the number of reports describing the beneficial effects of immunobiotics in diseases such as intestinal and respiratory infections, allergy, inflammatory bowel disease, obesity, immunosuppression, and several other immune-mediated conditions. Evidence is also emerging of immunobiotics related molecules with immunomodulatory functions leading to the production of pharmabiotics, which may positively influence human or animal health. Therefore, research in immunobiotics continue to contribute not only to food but also medical and pharmaceutical fields. The compilation of research articles included in this ebook should help reader to have an overview of the recent advances in immunobiotics.

Interaction of Nanomaterials with the Immune System: Role in Nanosafety and Nanomedicinenanomedicine

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453870 Year: Pages: 177 DOI: 10.3389/978-2-88945-387-0 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-11-16 17:17:57
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The immune system has the double role of maintaining tissue integrity and homeostasis and of protecting the organism from possible dangers, from invading pathogens to environmentally-borne dangerous chemicals. New chemicals recognisable by the immune system are engineered nanomaterials/ nanoparticles, new agents in our environment that are becoming common due to their presence in many products, from constructions and building material (e.g., solar cells, pigments and paints, tiles and masonry materials) to daily products (e.g., food packaging, cosmetics, and cigarettes). Human beings can be accidentally exposed to engineered nanomaterials when these are released from products containing them or during production in workplaces. Furthermore, intentional exposure occurs in medicine, as engineered nanoparticles are used as tools for improving delivery of drugs and vaccines, vaccine adjuvants and contrast agents in therapeutic, preventive and diagnostic strategies. Nanoparticles that come in contact with the immune system after unintentional exposure need to be eliminated from the organism as they represent a potential threat. In this case, however, due to their peculiar characteristics of size, shape, surface charge and persistence, nanoparticles may elicit undesirable reactions and have detrimental effects on the immune system, such as cytotoxicity, inflammation, anaphylaxis, immunosuppression. Conversely, nanomedicines need to escape immune recognition/elimination and must persist in the organism long enough for reaching their target and exerting their beneficial effects. Immune cells and molecules at the body surface (airway and digestive mucosae, skin) are the first that come in contact with nanomaterials upon accidental exposure, while immune effectors in blood are those that more easily come in contact with nanomedical products. Thus, evaluating the interaction of the immune system with nanoparticles/nanomaterials is a topic of key importance both in nanotoxicology and in nanomedicine. Immuno-nanosafety studies consider both accidental exposure to nanoparticles, which may occur by skin contact, ingestion or inhalation (at doses and with a frequency that are not known), and medical exposure, which takes place with a defined administration schedule (route, dose, frequency). Many studies focus on the interaction between the immune system and nanoparticles that, for medical purposes, have been specifically modified to stimulate immunity or to avoid immune recognition, as in the case of vaccine carriers/adjuvants or drug delivery systems, respectively. The aims of this Research Topic is to provide an overview of recent strategies: 1.for assessing the immunosafety of engineered nanomaterials/nanoparticles, in particular in terms of activation of inflammatory responses, such as complement activation and allergic reactions, based on the nanomaterial intrinsic characteristics and on the possible carry-over of bioactive contaminants such as LPS. Production of new nanoparticles taking into account their effects on immune responses, in order to avoid undesirable effects on one hand, and to design particles with desirable effects for medical applications on the other hand; 2.for designing more effective nanomedicines by either avoiding or exploiting their interaction with the immune systems, with particular focus on cancer diagnosis and therapy, and vaccination. This collection of articles gives a comprehensive view of the state-of-the-art of the interaction of nanoparticles with the immune system from the two perspectives of safety and medical use, and aims at providing immunologists with the relevant knowledge for designing improved strategies for immunologically safe nanomaterial applications.

Chocolate and Health: Friend or Foe?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454112 Year: Pages: 77 DOI: 10.3389/978-2-88945-411-2 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Nutrition and Food Sciences --- Medicine (General)
Added to DOAB on : 2018-11-16 17:17:57
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In the ancient past, cocoa has been appreciated as a high-calorie food to boost energy in soldiers and for its undefined medicinal and mystical properties. During other times, chocolate has been considered as the forbidden “food of God”: a treasure of pleasure for the mind and the soul. The overall perception of the consumer for chocolate was of a “charming” and appealing food with lots of negative aspects related to high sugar content leading to consider chocolate as “junk food” for its “obesigen” calories. Recently, in association with the renewed interest of nutrition science in alternative source of health-promoting foods and ingredients, a large body of research has been conducted to unravel the pro and cons of cocoa in relation to human health. Epidemiological evidences indicate that cocoa consumption helps preventing cardiovascular disease for its high content in bioactive flavonoids. Clinical trials show that chocolate consumption might improve vascular function, decreasing platelet aggregation and display an antioxidant and anti-inflammatory effect. The putative protective action of cocoa seems to be multi-factorial and involving different aspects of vascular, antioxidant and endothelial function. However, the mechanism(s) that account for the benefits of cocoa it is still unclear.The aim of this Research Topic is therefore to provide the reader with an objective picture of the state of art on the association between cocoa and health, mainly through the evidences of human trials; overwhelmingly considered the golden standard for nutritional science. The Research Topic will cover the analysis of the manufacturing processes of the chocolate and the antioxidant effects in humans as well as the majority of the putative health effects of chocolate and cocoa, such as anti-inflammatory properties, effect on immunity, platelet aggregation, blood pressure, endothelial function and cognitive behavior. Unraveling the functional properties of cocoa will help to understand if the 'food of God' is a primordial gift for the health of mankind.

Extracellular Vesicle-Mediated Processes in Cardiovascular Diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889456208 Year: Pages: 118 DOI: 10.3389/978-2-88945-620-8 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General)
Added to DOAB on : 2019-01-23 14:53:43
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It is long known that many cells can shed extracellular vesicles, small membrane-enclosed cell fragments. Although the existence of extracellular vesicles has been recognized for many years, researchers are only beginning to understand their physiologic significance. Several recent studies have demonstrated that extracellular vesicles released from cells serve as a mode of cellular communication. They can carry diverse molecular payload (e.g. nucleic acids, bioactive lipids and proteins) to distal organs and recipient cells. Extracellular vesicles can be classified into three major groups: exosomes, microvesicles, and apoptotic bodies. All these types of extracellular vesicles can be found in a variety of biologic specimen and their numbers, distribution and composition may serve as biomarkers for various disorders, including cardiovascular disease. Although extracellular vesicle-mediated processes are currently best characterized in the fields of cancer biology and neurobiology, evidence is accumulating that extracellular vesicles play a key role in the pathophysiology of diabetes, thrombosis, inflammation and cardiovascular calcification.In this Research Topic, we invited review and methodological articles that advance our understanding of extracellular vesicle-related processes in vascular biology.

Natural Killer Cells in Human Diseases: Friends or Foes?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454044 Year: Pages: 122 DOI: 10.3389/978-2-88945-404-4 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-11-16 17:17:57
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NK cells are lymphocytes of the innate immune system that share some features with adaptive immune cells like T cells. They are well known for their importance to control viral infections and tumor development, but also intracellular bacterial and parasitic infections. A balance between negative and positive signals transmitted via germ line-encoded inhibitory and activating receptors controls the function of NK cells. Activated NK cells respond by killing the infected or tumor cells without prior sensitization, and by producing cytokines and chemokines. It has been shown that NK cells cross-talk with other immune cells, such as dendritic cells and macrophages, can shape T cell and B cell immune responses through direct interactions as well as by virtue of their cytokine/chemokine production. NK cells can also regulate immune responses by killing other immune cells, including activated T cells, or by producing anti-inflammatory cytokines upon excessive inflammation. However, NK cells are not friends in all situations. Indeed, it has been shown in LCMV-infected murine models that, depending on the viral inoculation load, NK cells may either help fight infection or can promote chronic infection. Moreover in cancer models, it has been shown that NK cells can kill anti-tumoral T cells. Recent studies of NK cells in patients with cancer support the notion of detrimental roles of NK cells. Furthermore, studies implicate NK cells in contributing to both graft rejection and tolerance to an allograft. In some autoimmune diseases, like rheumatoid arthritis, NK cells may promote disease pathogenesis. The scope of this Research Topic is to present and discuss knowledge on the role of NK cells in various diseases settings: viral infections as well as other infections, cancer, transplantation, and autoimmunity. The aim is to discuss how NK cells respond during disease and specifically when, why and how NK cells can be harmful and if they exert different functions (production of specific cytokines, inhibition of other immune cells through other mechanisms beside cytotoxicity) in these situations. Which are the NK cell subsets that play beneficial or deleterious roles in these diseases? Are there different phenotypes associated with protective NK cells (e.g. antiviral, antitumoral) and NK cells involved in disease pathogenesis? How are these diverse NK cells activated and do they function primarily through direct cytotoxicity, ADCC or cytokine and chemokine production? What are the signals or interactions that can change and shape the NK cell response shifting them from protective to harmful? We thank the authors that submitted reviews and original research manuscripts that help to better understand these questions, with the aim that this will help the scientific community to determine what could be the main future research directions to better understand the role of NK cells in disease protection or development.

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