Neuro Immune Interactions In Inflammation And Autoimmunity

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.

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.

Brain-immune interactions are essential to maintain health and their dysfunction contributes to diverse human diseases. Recent data show that haematopoietic processes and immune organs are under central autonomic control. Deficient regulation of inflammatory events contributes to brain diseases, whereas acute or chronic brain injury is linked with the development of systemic inflammatory conditions or immunosuppression. At present, common disorders with high socio-economic burden such as cancer, cardiovascular-, neuroinflammatory- and neurodegenerative diseases, asthma, allergies, autism, psychiatric conditions and sepsis are believed to be influenced, at least in part, by the dysfunction of brain-immune communication. Since the median age of the world's population is increasing rapidly, it is expected that the burden of common non-communicable diseases will further increase, which represents a huge challenge to the health care systems worldwide. Thus, there is an increasing demand to understand and treat complex diseases, many of which are age-related, and this is not possible unless the fine-tuned communication between large systems -such as the nervous and the immune system- is comprehensively understood. Although it is impossible to cover all areas of relevant research in this field, papers in this eBook give some insight to a few important aspects of brain-immune interactions and their contribution to disease. We hope that this collection could stimulate further relevant research and facilitate discussions to support the understanding of the highly complex interactions between the immune system and the brain in health and disease.

It is now well appreciated that the immune system, in addition to its traditional role in defending the organism against pathogens, communicate in a well-organized fashion with the brain to maintain homeostasis and regulate a set of neural functions. Perturbation in this brain-immune interactions due to inflammatory responses may lead to psychiatric and neurological disorders. Microglia are one of the essential cells involved in the brain-immune interactions. Microglial cells are now not simply regarded as resident tissue macrophages in the brain. These cells are derived from myeloid progenitor cells in the yolk sac in early gestation, travel to the brain parenchyma and interact actively with neurons during the critical period of neurogenesis. Microglia provide a trophic support to developing neurons and take part in the neural wiring through the activity-dependent synapse elimination via direct neuron-microglia interactions. Altered microglial functions including changes in the gene expression due to early life inflammatory events or psychological and environmental stressors can be causally related to neurodevelopmental diseases and mental health disorders. This type of alterations in the neural functions can occur in the absence of infiltration of inflammatory cells in the brain parenchyma or leptomeninges. In this sense, the pathogenetic state underlying a significant part of psychiatric and neurological diseases may be similar to “para-inflammation”, an intermediate state between homeostatic and classical inflammatory states as defined by Ruslan Medzhitov (Nature 454:428-35, 2008). Therefore, it is important to study how systemic inflammation affects brain health and how local peripheral inflammation induces changes in the brain microenvironment. Chronic pain is also induced by disturbance in otherwise well-organized multisystem interplay comprising of reciprocal neural, endocrine and immune interactions. Especially, early-life insults including exposure to immune challenges can alter the neuroanatomical components of nociception, which induces altered pain response later in life. Recently the discrete roles of microglia and blood monocyte-derived macrophages are being defined. The distinction may be further highlighted by disorders in which the brain parenchymal tissue is damaged. Therefore, studies investigating the dynamics of immune cells in traumatic brain injury and neurotropic viral infections including human immunodeficiency virus, etc. as well as neurodegenerative diseases such as amyotrophic lateral sclerosis are promising to clarify the interplay between the central nervous and immune systems. The understanding of the histological architecture providing the infrastructure of such neuro-immune interplay is also essential. This Frontiers research topic brings together fourteen articles and aims to create a platform for researchers in the field of psychoneuroimmunology to share the recent theories, hypotheses and future perspectives regarding open questions on the mechanisms of cell-cell interactions with chemical mediators among the nervous, immune and endocrine systems. We hope that this platform would reveal the relevance of the studies on multisystem interactions to enhance the understanding of the mechanisms underlying a wide variety of neurological and psychiatric disorders.

The idea that the brain is an "immune-privileged site" has perhaps served to slow our realization that the intact brain can generate its own inflammatory reactions. These responses can be to peripheral infection, or they can arise from local, internal causes, for instance as a response to stress or to the se vere changes in neuronal activity in seizure or the loss of oxygen in stroke. We are also becoming increasingly aware of the contribution of local inflam matory reactions to certain neurodegenerative diseases such as Alzheimer's In fact, evidence is accumulating that inflammatory processes disease (AD). contribute to the progression of AD, suggesting the possibility of using cur rently available or novel anti-inflammatory agents to interfere with this terri ble disease. Correlations are also being made between inflammatory signs and mental illness, which is a new frontier of research. This book presents the current state of knowledge in a variety of areas relevant to neuro-immune interactions, with particular attention to AD.

Increasing evidence indicates that inflammatory cells and immunological cytokines can enter into the brain and modulate a number of biological and cognitive functions. Under physiological conditions, only a few immune cells, such as: macrophages, lymphocytes and dendritic cells can cross the blood-brain barrier and gain access to neural tissue. For many years, these findings supported the notion that the brain was an immunologically privileged organ. To date, increasing evidence strongly challenges this conjecture. In fact, neuroinflammation triggers a significant infiltration of immune cells into the cerebral parenchyma. The infiltration of inflammatory cells is accompanied by the release of a number of cytokines that target neurons, astrocytes and microglia. This interaction between the immune system and the central nervous system modulates many cerebral functions, such as: neural remodelling, synaptic plasticity, neurotransmitter releasing, stress-associated response, cognitive and mental disease progression, and others. The book summarises the latest discoveries, from basic to clinical science, regarding the interactions between the immunological mediators and the neural tissue under physiological and pathological conditions. In this book, it is discussed the influence of immune cells and cytokines in neural-regulated systems. Herein, the readers can find comprehensive descriptions in diverse fields, such as: lipids and obesity, neuronal activity, neurotransmission, stress pathogenesis, rheumatologic diseases, spinal cord injuries, regulation of neural stem cells, neural control of reproduction, and others. To ensure that most of readers obtain clear and complete information, all chapters have been written by prominent experts in their respective fields, who explain these topics with a very accessible language. In summary, this book represents a highly-updated compendium about the interactions between the central nervous system and the immune system that could be very useful for undergraduate students, postgraduate students, academic educators or trainers, basic science researchers and clinical physicians.

"Yet another cell and molecular biology book? At the very least, you would think that if I was going to write a textbook, I should write one in an area that really needs one instead of a subject that already has multiple excellent and definitive books. So, why write this book, then? First, it's a course that I have enjoyed teaching for many years, so I am very familiar with what a student really needs to take away from this class within the time constraints of a semester. Second, because it is a course that many students take, there is a greater opportunity to make an impact on more students' pocketbooks than if I were to start off writing a book for a highly specialized upper- level course. And finally, it was fun to research and write, and can be revised easily for inclusion as part of our next textbook, High School Biology."--Open Textbook Library.

The book Cell Interaction focuses on various processes that occur within and outside the cells. Cell interactions are important for functioning of many organ systems: cell adhesion, tissue development, cellular communication, inflammation, tumor metastasis, and microbial infection. Key features include developmental cell interactions, immune and neural cell interactions, cell interactions in normal and disease conditions and advanced level methods to evaluate cell interactions. This book will be a significant resource to all scientists and physicians who are intended to explore more on cells.