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.

This volume is a collection of articles written by Nobel Laureate Rita Levi-Montalcini and published from 1942 to 1995. Studies described in the first part set the stage for the discovery of a protein molecule which became known as the Nerve Growth Factor (NGF), described in detail in the second part. The NGF synthesized in minute amounts in all vertebrate tissues, plays an essential role in the differentiation and survival of several nerve cell populations in the peripheral and central nervous system. The discovery of the NGF was defined by the Nobel Foundation as a milestone in developmental neurobiology, and the author was awarded in 1986 with this prestigious award. Studies pursued in subsequent years and still in progress, have unveiled other fundamental properties of the NGF, described in the third part of this volume.

As lifespans increase, more people around the world find themselves victims of chronic pain. In spite of this, treatment options continue to be severely limited. Anti-inflammatory drugs can only do so much, while painkillers like opioids have led to crippling addictions and fatal overdoses. The subject of the book is the role of immune cells, including glial cells, and neuroimmune interactions in chronic pain. The book begins by examining the preclinical and clinical evidence supporting the involvement of non-neuronal cells in chronic pain. It discusses the interactions between non-neuronal cells and neurons in the regulation of chronic pain. It then presents the implications of these findings, including promising and emerging treatments such as specialized pro-resolving mediators (SPMs, such as resolvins and protectins), immune cell therapy, and complementary and alternative medicine, as well as neuromodulation and regenerative medicine, which may prove to be the turning point for hundreds of millions of patients world-wide who struggle to escape from the shadow of chronic pain. The book presents ground-breaking research that will alter current perspectives on chronic pain.

Psychoneuroimmunology is the first textbook to examine the complex functional relationships between the nervous system, the neuroendocrine and the immune system. The international leaders in this field have been brought together to create this pioneering text; each contributing from their area of expertise. The result is a comprehensive yet accessible interdisciplinary introduction to psychoneuroimmunology which also takes you further than the foundations of those fascinating topics by covering the most recent research in HIV/AIDS, autoimmune diseases, and the reactivation of latent herpes viruses. Attention is also given to the effects of behavior such as physical exercise, sleep, acute and chronic stress, and conditioning of immune functions in animals and humans. The whole is brought together with a wealth of cited research studies, and over 200 illustrations.

The second edition of Neuroimmune Pharmacology bridges the disciplines of neuroscience, immunology and pharmacology from the molecular to clinical levels with particular thought made to engage new research directives and clinical modalities. Bringing together the foremost field authorities from around the world, Neuroimmune Pharmacology will serve as an invaluable resource for the basic and applied scientists of the current decade and beyond.

This comprehensive and integrative book examines the role that infectious agents play in the etiology of various neuropsychiatric disorders, including schizophrenia, autism, mood disorders and obsessive-compulsive disorder. Recent advances in technology and methodology now afford a meaningful examination of the infectious etiologies of neuropsychia

Immune responses within the brain are still scarcely explored. Nerve tissue damage is accompanied by the activation of glial cells, primarily microglia and astroglia, and such activation is responsible for the release of cytokines and chemokines that maintain the local inflammatory response and actively recruit lymphocytes and monocytes to the damaged areas. Theoretically, these responses are designed to repair the brain damage. However, alterations, or a chronic perpetuation of these responses may underlie a number of neuro-pathologies. It is thought that each inflammatory scenario within the brain have a specific biochemical footprint characterized by the release of determined cytokines, chemokines and growing factors able to define particular immunological responses. Alongside, glial cells transform their cell body, become larger and develop higher number of branches adopting an active morphological phenotype. These changes are related with the search of interactions with other cells, such as bystander resident cells of the brain parenchyma, but also cells homing from the blood stream. In this process, microglia and astrocytes communicates with other cells by the formation of specific intercellular connections that are still poorly understood. These interactions are complex and entail the arrangement of cytoskeletal compounds, secretory and phagocytic domains. In this particular crosstalk there is a two-way communication in which glial cells and target cells come together establishing interfaces with specific information exchange. This way, glial cells orchestrate the particular response recruiting cellular subsets within the central nervous system and organizing the resolution of the brain damage. In this Frontiers Research Topic, we compile a selection of articles unfolding diverse aspects of glial-derived inflammation, focused on neurodegenerative diseases and other nervous system disorders, with special emphasis on microglia/macrophages as leading actors managing neuro-immunity.

Neuroimmunology is a rapidly growing emerging field at which two old sciences have converged to integrate two different types of responses into a single coherent response involving the coordinated action of both systems, neural and immune. During long time it was thought that both systems worked separately and in divergent pathways. The brain was considered an immunoprivileged site and the immune organs were deemed as independent of any neural influence and also of nervous innervation. Time has gone and has proven that the borders between both systems were merely artificial. Since the beginning of Neuroimmunology in the 1980s much work has been done to elucidate the gates and fences in neuro-immune interactions. Brain was shown to be under the continuous surveillance of the immune system, even under basal physiological conditions in the absence of any pathology. Likely, it was found a profuse nervous innervation of lymphoid organs and even of single immune cells. Gates for direct neural immune communication were found both centrally and peripherally. Centrally, the gates, but also the fences, were situated at the brain barriers, the blood-brain barrier and the blood-cerebrospinal fluid barrier, and at the circunventricular organs. Peripherally, the fences constituted the apparent diverse nature of molecules involved in neural and immune signaling; however, time proved that both system were capable of producing the same signaling molecules and also systematically responded to the molecules released by the other system. Therefore, the gates were open for direct neural-immune communication at the peripheral level. This Research Topic aimed to include original reports, reviews and technical reports regarding the description of the gates and fences in neural immune interactions. We intended to provide an extensive view of the mechanisms governing central and peripheral neural-immune interactions, and the role of the borders, the blood-neural barriers, in the regulation of the neural-immune communication.

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