Table of Contents
Overview
Definition and Scope
Neuroimmunology is a multidisciplinary field that integrates neuroscience, the study of the nervous system, and immunology, the study of the immune system. This discipline aims to elucidate the interactions between these two complex systems during various physiological processes, including development, homeostasis, and responses to injuries.[4.1] The scope of neuroimmunology encompasses the investigation of neuroimmune diseases, which are conditions that arise when the immune system erroneously attacks healthy components of the nervous system, such as in multiple sclerosis and neuromyelitis optica.[7.1] The historical roots of neuroimmunology can be traced back to the 19th century, with early descriptions of model diseases and the diagnostic examination of cerebrospinal fluid.[1.1] However, it was not until the early 1980s that neuroimmunology emerged as a distinct discipline, primarily focusing on autoimmune disorders affecting the nervous system.[2.1] The term "neuroimmunology" itself was first introduced in the scientific literature in 1982, coinciding with the inaugural Neuroimmunology Congress held in Stresa, Italy.[3.1] Neuroimmunologists investigate the critical crosstalk between immune cells and the central nervous system (CNS), which is essential for proper CNS development, pathogen clearance, and the resolution of inflammation.[5.1] This research area is rapidly evolving, with a long-term goal of enhancing our understanding of the pathophysiology of chronic inflammatory diseases, particularly neuroinflammation.[6.1] Through this interdisciplinary approach, neuroimmunology seeks to provide insights into the complex interplay between the nervous and immune systems, ultimately aiming to improve treatment strategies for neuroimmune disorders.[6.1]Importance of Neuroimmunology
The field of neuroimmunology is essential for understanding the intricate interactions between the immune system and the central nervous system (CNS), particularly in the context of various neurological disorders. This interaction is significant in maintaining healthy brain function and contributing to the pathogenesis of neurodegenerative diseases such as multiple sclerosis (MS) and other neuroinflammatory conditions.[12.1] Recent research has highlighted the role of innate immune cells, including microglia, macrophages, and astrocytes, which operate independently of lymphocytes and may influence the progression of primary neurodegenerative diseases.[10.1] The relationship between the immune system and the nervous system is complex and plays a pivotal role in many disorders, especially neurodegenerative diseases.[11.1] The central diffuse immunomodulatory system and neuro-immunological memory are implicated in neuroimmune-related disorders, suggesting that peripheral immune responses may arise from pathogenic alterations or central immune responses.[9.1] As the field evolves, there is an urgent need for interdisciplinary research and the application of novel technologies to further explore neuroimmune interactions.[11.1] Integrating neuroimmunology findings into clinical practice is expected to improve patient treatment protocols and outcomes. For instance, the development of biomarkers for treatment and optimization of patient selection can enhance the benefit-to-risk ratio for individual therapies.[15.1] In addition, increased awareness and education about neuroimmune diseases can significantly impact the quality of life for patients. Initiatives such as the Siegel Rare Neuroimmune Association's Online Learning Program aim to empower individuals with knowledge about conditions like acute disseminated encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorder (NMOSD), providing essential tools for navigating their health challenges.[22.1]History
Key Milestones in Neuroimmunology
The field of neuroimmunology has evolved significantly over the past century, marked by several key milestones that have shaped its development. Its origins can be traced back to the 19th century, where early observations linked neurological diseases with immune responses, particularly through the study of model diseases such as multiple sclerosis and Guillain-Barré syndrome. The diagnostic examination of cerebrospinal fluid by Quincke was pivotal in establishing the connection between the nervous and immune systems.[1.1] The term "neuroimmunology" was first introduced in the early 1980s, coinciding with the inaugural Neuroimmunology Congress held in Stresa, Italy, in 1982. This event marked the formal recognition of neuroimmunology as a distinct scientific discipline, primarily focusing on autoimmune disorders affecting the nervous system.[3.1] Since then, the field has expanded rapidly, driven by increasing evidence of the immune system's role in neurological and psychiatric disorders, as well as the nervous system's influence on immune function.[58.1] A significant review by Sandra Amor and colleagues highlighted critical technical, experimental, and clinical milestones that have contributed to the field's growth.[49.1] The recognition of bidirectional communication between the nervous and immune systems has been a central theme, emphasizing the importance of understanding how these systems interact in various contexts, such as development and aging.[58.1] Recent advancements in technology, including sophisticated imaging techniques and high-throughput methodologies, have further propelled the field, allowing for unprecedented insights into the mechanisms underlying neuroimmune interactions.[60.1] These developments have opened new avenues for therapeutic strategies targeting microglia, meningeal lymphatics, and the peripheral immune system, which may lead to effective treatments for a range of central nervous system disorders.[61.1]Recent Advancements
Current Research Trends
Recent advancements in neuroimmunology have reshaped our understanding of the central nervous system (CNS), highlighting its role as an active immune organ. This field explores the interactions between immune and central nervous system cells, which are crucial for CNS development, pathogen clearance, and inflammation resolution.[89.1] Integrating these insights into clinical practice is evolving, with a transformative framework proposed to enhance patient outcomes through personalized treatment for neuroimmune diseases.[97.1] Current research trends focus on elucidating mechanisms underlying neuroimmune diseases, such as multiple sclerosis (MS), where the immune system mistakenly targets nervous system components. Studies emphasize the importance of immune system communication in maintaining CNS health, with disruptions leading to autoimmunity and neurodegeneration.[92.1] The role of epigenetic mechanisms in autoimmunity development is gaining attention, suggesting new therapeutic avenues.[92.1] Novel technologies are enhancing data integration, improving our understanding of disease mechanisms and patient variability.[96.1] As noted by Dr. Erin Longbrake, there is a surge in treatment options for neuroimmune diseases, with ongoing research uncovering previously unrecognized aspects.[94.1] This includes clinical trials testing innovative treatments for MS and other conditions, emphasizing personalized therapies.[94.1] Research highlights the critical role of immune cell interactions in MS pathophysiology, suggesting that understanding these interactions could lead to more targeted treatments.[99.1] Continued collaboration in neuroimmunology is essential for enhancing patient outcomes and integrating therapeutic developments into clinical practice.[100.1] Advancements in diagnostic tests for neuroimmunological disorders are crucial for improving clinical practice. Dr. John Mills from the Mayo Clinic emphasizes the need for effective diagnostic tests to enhance patient care.[98.1] The Mayo Clinic Laboratories are pioneering this field with specialized tests, allowing for accurate diagnoses and tailored treatment strategies.[98.1] Ongoing research in neuroimmunology is vital for developing personalized and effective treatments, underscoring the importance of continued research and collaboration.[100.1]Emerging Therapeutic Approaches
Recent research in neuroimmunology has led to the development of several promising therapeutic approaches, particularly in the context of multiple sclerosis (MS) and other neuroimmune diseases. The immunopathogenic model of MS highlights the interplay between genetic and environmental factors that activate myelin-reactive T cells, underscoring the importance of immune cell interactions in disease progression.[107.1] This understanding has paved the way for targeted therapies focusing on specific immune mechanisms involved in inflammation and demyelination, potentially improving patient outcomes.[107.1] Advancements include therapies targeting various phases of inflammation, offering remyelinating strategies, and providing neuroprotective effects aimed at oligodendrocytes, crucial for myelin repair.[109.1] Additionally, exploring genetic risk variants has revealed their influence on pre-mRNA splicing, which may inform future treatment strategies.[108.1] Clinical trials, such as the OzEAN study, are investigating the long-term safety and efficacy of new treatments like ozanimod for relapsing-remitting MS, contributing to a growing body of evidence supporting innovative therapeutic options.[108.1] Moreover, emerging therapies are being developed to address neurodegenerative diseases through strategies targeting the accumulation of misfolded proteins and oligomers, implicated in neuronal toxicity.[118.1] These immunotherapeutic approaches aim to clear or inhibit the formation of such aggregates, showing promise in clinical settings.[118.1] Despite these advancements, challenges remain in translating neuroimmunology research into effective treatment strategies. The complexity of neuroimmune interactions necessitates a deeper understanding of the bidirectional communication between the immune system and the nervous system.[124.1] Furthermore, translating biomarker discoveries from population averages to individual patient care continues to be a significant hurdle.[126.1] Collaborative efforts among researchers, clinicians, and stakeholders are essential to bridge these gaps and enhance the precision of neuroimmunological therapies.[125.1]In this section:
Neuroimmune Interactions
Mechanisms of Communication
Neuro-immune interaction involves the intricate communication between the nervous and immune systems, where each system influences the other's functions and responses. This interaction is crucial in various pathological conditions, such as neurodegenerative diseases, stroke, and infections, underscoring the importance of understanding these mechanisms for therapeutic advancements.[134.1] Recent research highlights the role of cytokines as key mediators in neuroimmune interactions. These soluble factors, produced by immune cells, modulate the immune response and influence neuronal behavior even in the absence of infection.[175.1] Cytokines such as TNF-α regulate inflammation, cell proliferation, and apoptosis, affecting both immune and neural functions.[174.1] Additionally, neuroimmune cell units, where neuronal and immune cell subsets colocalize, facilitate bidirectional interactions essential for maintaining tissue homeostasis and responding to injury.[172.1] Neuroinflammation is a response of reactive components within the central nervous system (CNS) to altered homeostasis, which can arise from both endogenous and exogenous factors.[136.1] This inflammatory response is a critical aspect of neuroimmune interactions, involving complex mechanisms that vary across different tissues and contexts.[135.1] Neuroimmune diseases, such as multiple sclerosis, occur when the immune system mistakenly attacks healthy parts of the nervous system, leading to various neurological conditions that affect the brain, spinal cord, and nerves.[137.1] Each type of neuroimmune condition presents different symptoms depending on the specific areas of the nervous system targeted during inflammation.[137.1] Understanding these interactions is essential for developing effective treatment options for complex neuroimmune diseases that impact CNS function.[137.1]Role in Health and Disease
Neuroimmune interactions are crucial in both health and disease, particularly concerning neurological disorders and psychiatric conditions. The immune system's influence on brain health has been increasingly recognized, suggesting that understanding these interactions can lead to improved therapeutic strategies for various neuroimmunological disorders, including multiple sclerosis (MS) and psychiatric illnesses such as depression and schizophrenia.[145.1] In multiple sclerosis, the interaction between immune cells and the central nervous system (CNS) is pivotal. Studies highlight the importance of specific immune cell types, cytokines, and chemokines in driving inflammation and demyelination, which are fundamental to MS pathophysiology.[140.1] This understanding opens avenues for targeted therapies that could mitigate the disease's progression by addressing the underlying immune dysregulation.[140.1] Neuroimmune interactions also play a significant role in psychiatric disorders, emphasizing immune dysregulation in conditions such as schizophrenia, autism spectrum disorder, bipolar disorder, and depression.[143.1] For instance, depression is closely linked to the two-way communication between the immune system and the brain. Studies indicate that cognitive impairments associated with depression can be influenced by mature T cells; experiments have shown that cognitive abilities in mice were impaired in the absence of these cells, but this effect could be restored through passive T-cell transfer.[144.1] This understanding has led to the recognition that managing these multifactorial mental disorders requires an integrated therapeutic approach, which may include targeting the neuroinflammatory response in the CNS using existing immunomodulatory and anti-inflammatory drugs or medical foods.[142.1] Overall, neuroimmunology represents a promising frontier in understanding and treating psychiatric disorders, significantly shifting the paradigm of mental health research by emphasizing the immune system's role in brain function and pathology.[145.1] Astrocytes and microglia are essential immune cell types in the CNS that play significant roles in neuroinflammation and its implications for neurodegenerative diseases. Astrocytes regulate both innate and adaptive immune responses in the injured CNS. Depending on their activation context, astrocytes can either exacerbate inflammatory reactions and tissue damage or promote immunosuppression and tissue repair.[148.1] Similarly, microglia exhibit dual roles; they drive the pathological hallmarks of neuroinflammation while also preserving and repairing damaged tissue, particularly in conditions such as stroke and Alzheimer's disease.[149.1] The interplay between microglia and astrocytes, often referred to as microglia-astrocyte crosstalk, is vital for the CNS's response to various insults, injuries, or inflammatory stimuli.[151.1] Furthermore, the complexity of microglial and astrocytic phenotypes, along with the varying stages of neurodegenerative diseases, underscores the importance of understanding their roles in the context of pro-inflammatory cytokines and the potential benefits of anti-inflammatory treatments in clinical trials.[150.1] Moreover, the gut-immune-brain axis is emerging as a critical area of research, with studies suggesting that gut microbiota may influence CNS inflammatory diseases and overall brain physiology.[141.1] This highlights the complexity of neuroimmune interactions and their implications for understanding and treating neurodegenerative diseases, where inflammation is a common pathological feature.[152.1]Neuroimmunological Disorders
Autoimmune Conditions
Autoimmune conditions in neuroimmunology involve the immune system mistakenly attacking healthy components of the nervous system, leading to various neurological disorders. Multiple sclerosis (MS) is a notable example, where the immune system targets the central nervous system (CNS), causing a range of symptoms that vary among individuals based on the specific areas affected during inflammation.[177.1] Diagnosing neuroimmunological disorders requires a comprehensive clinical evaluation and targeted diagnostic testing, including neurophysiologic assessments, neuroimaging, blood tests, and sometimes cerebrospinal fluid analysis.[178.1] Treatment typically involves creating a personalized plan addressing the specific immune-related condition affecting the central and peripheral nervous systems, as symptoms can differ significantly from patient to patient.[179.1] Healthcare providers collaborate closely with patients to develop individualized treatment strategies that meet their unique needs.[196.1] Autoimmune neurological disorders present a diverse range of symptoms, complicating early diagnosis.[183.1] In pediatric patients, the clinical presentation is particularly variable, often involving cognitive, memory, and behavioral impairments, as well as movement disorders; notably, refractory or super-refractory status epilepticus is frequently observed in this population.[183.1] The clinical phenotypes of patients with common variable immunodeficiency (CVID) also demonstrate significant variability, with a small percentage of cases attributed to heritable causes, while the majority are polygenic or multifactorial.[184.1] This variability underscores the complexity of neuroimmunological disorders and highlights the necessity for comprehensive assessment and diagnosis.[184.1] The pathogenesis of neuroimmunological disorders is significantly influenced by specific immune cells, particularly B cells and T cells. B cells not only produce antibodies but also play critical roles in regulating T-cell responses and maintaining immune homeostasis.[191.1] T cells, especially subsets like FOXP3 + CD25 + CD4 + regulatory T cells, are essential for suppressing autoimmunity and mediating self-tolerance.[193.1] In MS, T cells are known to produce proinflammatory cytokines that contribute to the disease's progression.[194.1] An interdisciplinary approach is crucial for delivering comprehensive care to individuals with MS and other complex neuroimmunological conditions. This model emphasizes team-based research to enhance patient-centered care for all affected individuals.[195.1] Given the variety of immune-related conditions impacting different parts of the central and peripheral nervous system, symptoms can differ significantly from one patient to another. Therefore, care teams must collaborate closely with patients to develop tailored treatment plans that address their specific disorders and unique needs.[196.1]Neurodegenerative Diseases
Neurodegenerative diseases (NDs) are marked by chronic neuroinflammation, significantly contributing to their progression. Neuroinflammation is a complex response of the central nervous system (CNS) to various insults, such as injury and infection. While acute neuroinflammation aids in pathogen clearance and tissue repair, its chronic and dysregulated form is linked to the advancement of disorders like Alzheimer's disease and Parkinson's disease.[201.1] Recent research highlights the critical role of immune cells in neuroinflammation associated with NDs. Microglia, the brain's primary resident immune cells, become activated in response to neurodegenerative processes.[187.1] Peripheral immune cells can infiltrate the brain, transforming microglia into a pro-inflammatory phenotype, potentially accelerating disease progression.[202.1] Additionally, immune cells in non-parenchymal regions at the brain's borders are crucial for maintaining neuronal health, responding to injury, and regulating CNS inflammation.[187.1] Understanding these interactions is vital for developing targeted therapies for neuroimmunological disorders.[186.1] Dysregulation of the immune system is a pathological hallmark across nearly all neurodegenerative diseases.[189.1] This dysregulation often results in elevated levels of pro-inflammatory cytokines, such as TNF-α and IL-1β, especially in aging, which further promotes neuroinflammation.[212.1] The integrity of the blood-brain barrier (BBB) is also crucial; its compromise allows peripheral immune cells to infiltrate the CNS, exacerbating neuroinflammation and cognitive decline.[214.1] Advancements in gene therapy targeting neuroinflammation offer promising therapeutic avenues for NDs. Although still in early stages, insights from other disorders may enhance the translational potential of gene therapy for neurodegenerative conditions.[185.1] Recent findings suggest that targeting specific pathways, such as PI3K/Akt, STAT1/3, and NF-κB signaling pathways, can attenuate microglial activation and neuronal damage, indicating potential strategies for managing neuroinflammation-related diseases.[200.1]Methodologies In Neuroimmunology Research
Immunological Assays
Neuroimmunology research utilizes a range of immunological assays that integrate techniques from both immunology and neuroscience, alongside methods standard in fields like genetics and cellular biology. These assays are meticulously chosen to highlight specific outcomes while reducing confounding variables, thereby improving the reliability of the results.[219.1] Emerging methodologies, particularly multiomics approaches, represent a significant advancement over traditional methods that typically focus on individual pathways or genes. Multiomics methodologies enable a comprehensive examination of multiple immune-signaling pathways, allowing researchers to test hypotheses and evaluate therapeutic effects at a systems level.[243.1] Unlike the traditional single-omics approach, which examines biological processes from a genomics or transcriptomics perspective, multiomics methods explore interactions across various biological domains, producing comprehensive biological insights.[244.1] This shift enhances our understanding of neuroimmunological interactions by integrating diverse data types and revealing complex interdependencies within immune signaling networks. The bidirectional communication between the immune system and the central nervous system (CNS) is a critical focus in neuroimmunology. This interaction is mediated by immune mediators and cytokines that can traverse the blood-brain barrier or signal indirectly via the vagus nerve, illustrating the intricate interplay between these systems.[225.1] Inflammatory responses are crucial for antimicrobial defense and tissue repair; however, improper regulation can lead to tissue damage and exacerbate neuronal injury, contributing to disease progression.[227.1] Understanding these mechanisms is vital, as chronic immune cell activation and persistent inflammation can significantly influence the course of chronic inflammatory diseases.[227.1] Advancements in technology are essential for non-invasively assessing neuroimmune interactions in both animal models and humans, which is crucial for translating research findings into effective treatments.[217.1] Investigating how immune status, particularly from the gastrointestinal tract, is represented in the brain and how this information regulates the gastrointestinal system is an emerging area of interest, highlighting the complexity of neuroimmune interactions.[218.1]Future Directions
Challenges and Opportunities
The field of neuroimmunology is confronted with significant challenges and opportunities in understanding and addressing the complexities of neuroinflammatory diseases. A primary challenge is the multifactorial etiology and heterogeneous progression of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).[274.1] These disorders exhibit diverse pathological manifestations, complicating the development of effective therapeutic strategies. The immune system's role in neurodegeneration is increasingly recognized, with recent evidence suggesting a more nuanced contribution than previously understood, necessitating further investigation into the mechanisms underlying neuroinflammation.[275.1] Integrating immunotherapy approaches in treating neuroinflammatory diseases presents both challenges and opportunities. Current therapies, primarily delivered through infusion methods, may not effectively reach critical immune compartments involved in disease progression.[276.1] Identifying key immunological niches is crucial for enabling compartment-specific therapeutic delivery. Passive immunization strategies, such as anti-GA RAN antibodies, have shown effectiveness in reducing neuroinflammation and neurodegeneration in preclinical models, highlighting the potential for further exploration of immunotherapeutic avenues to enhance treatment efficacy.[277.1] The gut-brain axis is an emerging research area, with evidence indicating that gut microbiota influence neuroinflammation and may serve as therapeutic targets.[265.1] This interplay emphasizes the importance of a healthy gut microbiome for overall immune and neurological health, presenting new opportunities for therapeutic strategies that could slow disease progression and improve patient outcomes.[267.1] As research evolves, understanding the effects of dietary components and microbial metabolites on host physiology will be crucial for developing innovative treatments.[268.1]Interdisciplinary Collaborations
Interdisciplinary collaboration is crucial in the treatment of neuroinflammatory diseases, offering a comprehensive approach to complex health issues. This collaboration involves various specialists, including primary care physicians, nursing staff, and specialists within accountable care organizations. Such a model improves patient outcomes and reduces healthcare costs by fostering effective communication and coordinated care among healthcare providers.[286.1] The complexity of multisystem syndromes, with overlapping symptoms across specialties, underscores the need for interdisciplinary approaches. For example, a cardiologist may identify cardiovascular manifestations of an autoimmune disease with neurological implications, necessitating collaboration between disciplines for comprehensive patient care.[287.1] The future of neuroimmunology will likely be shaped by breakthroughs from collaborative networks integrating fields such as immunology, neuroscience, hematology, genetics, computer science, physics, bioengineering, drug development, and clinical research. These efforts are expected to enhance our understanding of the blood-brain-immune interface, leading to more effective treatments for neuroinflammatory conditions.[288.1] Furthermore, interdisciplinary collaboration is vital for advancing the understanding and management of neuroinflammatory diseases. It addresses the complex ethical and societal implications of neuroinflammation research and enhances treatment strategies. By integrating insights from various scientific domains, researchers can better tackle the multifaceted challenges posed by these conditions, ultimately improving patient outcomes.[285.1]In this section:
References
[1] Neuroimmunology Research. A Report from the Cuban Network of ... — A first topic addressed was to review some events on the history of neuroimmunology. This talk fixed the roots of neuroimmunology in the 19th century, with the descriptions of some of the model diseases (e.g., multiple sclerosis, neuromyelitisoptica, Guillain-Barré syndrome), the diagnostic examination of cerebrospinal fluid (CSF) by Quincke
[2] A neuroimmune odyssey - Nature Reviews Immunology — Neuroimmunology first emerged as a discipline in its own right in the early 1980s. For many years, the field was dominated by studies of autoimmune disorders that affect the nervous system, such
[3] Neuroimmunology - the past, present and future - Wiley Online Library — History o euroimmunology NEUR-IMMUN INTEACTINS HW TH NERVOUS AN IMMUN SYSTES INFLUENC ACH THER Despite this evidence, it is surprising that the term 'neuroimmunology' was only first used on PubMed in 1982, coinciding with the first Neuroimmunology Congress in Stresa, Italy (Fig. 1) and following the launch of the
[4] Neuroimmunology - Wikipedia — Neuroimmunology is a field combining neuroscience, the study of the nervous system, and immunology, the study of the immune system.Neuroimmunologists seek to better understand the interactions of these two complex systems during development, homeostasis, and response to injuries.A long-term goal of this rapidly developing research area is to further develop our understanding of the pathology
[5] An Introduction to Neuroimmunology - PMC - PubMed Central (PMC) — Neuroimmunology encompasses a broad and ever-expanding discipline that centers on the interactions between cells of the immune and central nervous systems. This crosstalk is critical for proper CNS development, surveillance, clearance of pathogens, and the resolution of inflammation. During aberrant inflammatory processes and neurodegeneration
[6] Neuroimmunology - an overview | ScienceDirect Topics — Abstract. Neuroimmunology is a research field that intersects neuroscience and immunology, with the larger aim of gaining significant insights into the pathophysiology of chronic inflammatory diseases such as multiple sclerosis. Conventional studies in this field have so far mainly dealt with immune responses in the nervous system (i.e. neuroinflammation) or systemic immune regulation by the
[7] Neuroimmunology: What It Is & Disorders - Cleveland Clinic — There are several neurological conditions that happen as a result of your immune system attacking healthy parts of your nervous system like multiple sclerosis. What are neuroimmune diseases (neuroimmunological disorders)? Neuroimmune diseases are conditions that affect your brain, spinal cord and nerves (neurological conditions) and happen after your immune system mistakenly attacks part of your nervous system. Each type of neuroimmune condition has different symptoms depending on what part of your nervous system your immune system targets during inflammation. They may work closely with your current care team to find treatment options for complex neuroimmune diseases that affect how your nervous system functions. Neuroimmunologists study neuroimmunology, or the link between your nervous and immune systems.
[9] Neuroimmune interactions and their roles in neurodegenerative diseases ... — For instance, in neurodegenerative diseases, peripheral immune responses could be the outcome of pathogenic alterations or central immune responses of the central diffuse immunomodulatory system. If this is the case, the central diffuse immunomodulatory system and neuro-immunological memory may also take part in neuroimmune-related disorders.
[10] Neurology® Neuroimmunology and Neuroinflammation Enters Its Second ... — Recently, the field of neuroimmunology has seen a rapid growth in publications focused on innate immune cells (e.g., microglia, macrophages, and astrocytes) and how, independent of lymphocytes, those cells may contribute to the progressive phase of MS, primary neurodegenerative diseases, and other neuroinflammatory conditions.
[11] Neuroimmune interactions and their roles in neurodegenerative diseases ... — In conclusion, the interplay between the nervous system and the immune system is intricate and delicate and plays a pivotal role in many disorders, especially neurodegenerative diseases . To further discover neuroimmune interactions, more in-depth collaborative interdisciplinary research and novel state-of-the-art technologies are urgently needed.
[12] The interplay between the immune and central nervous systems in ... — The interplay between components of the immune system and CNS contributes both to healthy brain function and to the pathogenesis of neurodegenerative diseases such as multiple sclerosis. ... Wekerle H, Hohlfeld R. Neurotrophic cross-talk between the nervous and immune systems: implications for neurological diseases. Ann Neurol 2003;53:292-304
[15] Management of disease-modifying treatments in neurological autoimmune ... — Optimization of the benefit-to-risk ratio for individual substances can be achieved on multiple levels, including (a) patient selection according to clinical/paraclinical criteria, (b) optimization of treatment and monitoring protocols, (c) identification of patients at higher risk for SADRs and (d) the development of biomarkers for treatment
[22] Announcing the First Online Micro-Course for Rare Neuroimmune ... - SRNA — Education and knowledge are key in empowering those living with conditions like acute disseminated encephalomyelitis (ADEM), acute flaccid myelitis (AFM), MOG antibody disease (MOGAD), neuromyelitis optica spectrum disorder (NMOSD), optic neuritis (ON), and transverse myelitis (TM), providing them with the necessary tools to navigate the highs and lows that come with having a rare neuroimmune
[49] Neuroimmune interactions: how the nervous and immune systems influence ... — The Review series starts with a state-of-the-art review by Sandra Amor and colleagues regarding the past, present and future of the field of neuroimmunology. They provide a fascinating overview of key technical, experimental and clinical milestones and findings in the field that paved the way for some of the insights described above.
[58] Research priorities for neuroimmunology: identifying the key research ... — Neuroimmunology represents a rapidly expanding area of research with a high potential to improve human health, catalysed by increasing evidence implicating the immune system in neurological and psychiatric development and disorders and, conversely, the role of the nervous system in modifying immune function. The authors propose ten questions within four different frameworks: (a) The context of understanding the importance of bidirectional communication (e.g., afferent vs efferent); (b) Deciphering whether neuroimmune crosstalk is more important in some contexts that others (e.g., development vs aging) and the contribution of co-morbidities; (c) The need for advancement and development of newer technologies to non-invasively assess neuroimmune interactions in animals and humans; and (d) The importance of translating answers to these ten fundamental questions into treatments that help patients. Although top-down (efferent) pathways are mentioned, the clear focus of this article is on bottom-up communication from the immune system to the brain, with the aim of improving/understanding/treating mental health disorders.
[60] Reimagining the meninges from a neuroimmune perspective: a boundary ... — This surge in neuroimmune research has fundamentally reshaped our understanding of the meninges [1, ... opening new avenues for research and potential therapeutic strategies in neurological disorders. ... Recent advances in neuroimmunology, genetics, and imaging techniques have revolutionized our understanding of meningeal immunity.
[61] Updating Neuroimmune Targets in Central Nervous System Dysfunction — Here, we review recent advances in the field of neuroimmunology and discuss novel strategies for targeting microglia, meningeal lymphatics, and the peripheral immune system that may lead to successful treatment of a broad range of CNS disorders. ... (HCT) has emerged as a novel therapy for selected neurological disorders, including certain
[89] An introduction to neuroimmunology - Wiley Online Library — Neuroimmunology encompasses a broad and ever-expanding discipline that centers on the interactions between cells of the immune and central nervous systems. This crosstalk is critical for proper CNS development, surveillance, clearance of pathogens, and the resolution of inflammation. During aberrant inflammatory processes and
[92] Neuroimmunology - Wikipedia — Throughout development and adult life, the immune system detects and responds to changes in cell identity and neural connectivity. Deregulation of both adaptive and acquired immune responses, impairment of crosstalk between these two systems, as well as alterations in the deployment of innate immune mechanisms can predispose the central nervous system (CNS) to autoimmunity and neurodegeneration. Other evidence has shown that development and deployment of the innate and acquired immune systems in response to stressors on functional integrity of cellular and systemic level and the evolution of autoimmunity are mediated by epigenetic mechanisms. Autoimmunity has been increasingly linked to targeted deregulation of epigenetic mechanisms, and therefore, use of epigenetic therapeutic agents may help reverse complex pathogenic processes. Multiple sclerosis (MS) is one type of neuroimmunological disorder that affects many people.
[94] What Is Neuroimmunology? > News - Yale Medicine — “We've had an explosion of treatment options for known neuroimmune diseases, but we are also uncovering new aspects of diseases that we previously did not know had a neuroimmunology connection,” says Erin Longbrake, MD, PhD, a Yale Medicine neuroimmunologist. For example, if someone has lupus (a disease in which the immune system produces antibodies against its own cells and tissues, leading to widespread inflammation and tissue damage) and the disease appears to be affecting the brain, they might see a neuroimmunologist, who can manage their neurological symptoms. Yale (and other academic medical institutions) now offer numerous clinical trials testing treatments that could help with MS and other neuroimmune conditions, Dr. Longbrake says.
[96] Navigating the Neuroimmunomodulation Frontier: Pioneering Approaches ... — The advent of novel technology has fueled recent advancements in neuroimmunology by providing a more human ... and Susac syndrome. Under such circumstances, these technologies facilitate the integration of data from ... not all drugs targeting neuroimmune signaling have translated well into clinical practice. For instance, CCR2
[97] Revolutionizing Neuroimmunology: Unraveling Immune Dynamics and ... — Neuroimmunology is reshaping the understanding of the central nervous system (CNS), revealing it as an active immune organ rather than an isolated structure. ... By synthesizing these advancements, we propose a transformative framework that integrates cutting-edge research with clinical translation, charting a bold path toward redefining CNS
[98] Integration, innovation, precision: Propelling leading-edge diagnostics — “The clinician is limited when they don't have a good diagnostic test,” says Dr. John Mills, co-director of the Clinical Neuroimmunology Laboratory at Mayo Clinic. “The value of integration is that we’re always asking questions for patients: are we barking up the right tree, do we have the right test for that, do we have to create something new?” says William Morice II, M.D., Ph.D., CEO and president of Mayo Clinic Laboratories. At present, of the 30-plus antibodies the neuroimmunology lab has tests for, more than five are only available at Mayo Clinic Laboratories because they are new or rare discoveries, Dr. Mills adds. Learn more about Autoimmune Neurology Testing at Mayo Clinic Laboratories.
[99] A Comprehensive Review on Neuroimmunology: Insights from Multiple ... — Articles meeting certain criteria were selected for inclusion: studies or research articles focused on neuroimmunology; publications providing insight into pathophysiology, etiology, clinical aspects, and immunology implications related to multiple sclerosis as they apply to neuroimmunology; clinical trials/experimental/observational research investigating therapeutic developments/interventions regarding MS/related neuroinflammatory conditions; and publications available either in English or with accessible English translations to ensure comprehension. So, MS research highlights the critical role played by immune cell interactions in the development of multiple sclerosis (MS). (a)Uncovering Underlying Mechanisms: Exploring the interrelations between MS’s immune and neurological systems can provide insight into specific physiological and molecular processes driving disease development while pinpointing key immune cell types, cytokines, and chemokines associated with inflammation and demyelination, which will allow targeted therapies;
[100] A Comprehensive Review on Neuroimmunology: Insights from Multiple ... — In conclusion, this review underscores neuroimmunology's significance in MS research, suggesting that a deeper understanding could pave the way for more tailored and effective treatments for MS and similar conditions. Continued research and collaboration in neuroimmunology are essential for enhancing patient outcomes.
[107] A Comprehensive Review on Neuroimmunology: Insights from Multiple ... — Articles meeting certain criteria were selected for inclusion: studies or research articles focused on neuroimmunology; publications providing insight into pathophysiology, etiology, clinical aspects, and immunology implications related to multiple sclerosis as they apply to neuroimmunology; clinical trials/experimental/observational research investigating therapeutic developments/interventions regarding MS/related neuroinflammatory conditions; and publications available either in English or with accessible English translations to ensure comprehension. So, MS research highlights the critical role played by immune cell interactions in the development of multiple sclerosis (MS). (a)Uncovering Underlying Mechanisms: Exploring the interrelations between MS’s immune and neurological systems can provide insight into specific physiological and molecular processes driving disease development while pinpointing key immune cell types, cytokines, and chemokines associated with inflammation and demyelination, which will allow targeted therapies;
[108] Editorial: Insights in multiple sclerosis and neuroimmunology: 2021 — In the article “Genetic risk variants for multiple sclerosis are linked to differences in alternative pre-mRNA splicing” by Putscher et al., the authors show that genetic variants from MS risk loci affect pre-mRNA splicing. In the article “Peptidylarginine deiminase 2 autoantibodies are linked to less severe disease in multiple sclerosis and post-treatment Lyme disease,” Kim et al. present their real-world and long-term study “OzEAN study to collect real-world evidence of persistent use, effectiveness, and safety of ozanimod over 5 years in patients with relapsing-remitting multiple sclerosis in Germany.” The results of this study will add to the safety profile and efficacy profile of ozanimod in the treatment of RRMS.
[109] Recent advances in the treatment of primary and ... - ScienceDirect — The article highlights upcoming potential treatments, which target different phases of inflammation and offer remyelinating strategies as well as direct and indirect neuroprotective and oligodendrocyte protective effects, providing a hopeful outlook for patients with primary and secondary progressive multiple sclerosis (PPMS and SPMS).
[118] Immunotherapy: An emerging treatment option for neurodegenerative diseases — Most of the proteins undergoing such conformational transition are natively disordered, and the contribution of smaller aggregates (oligomers) vis-à-vis the larger ones in causing neuronal toxicity is still a matter of discussion.(p20),(p21) Different causes have been proposed for the toxicity of oligomers, such as permeabilization of the lipid membrane, disruption of calcium signalling, endoplasmic reticulum stress, proteasome impairment, mitochondrial dysfunction, disturbances of autophagy, etc.(p22),(p23),(p24) Activation of distinct components of both innate and adaptive arms of the immune system has been seen upon accumulation of non-native or misfolded proteins in the brain.(p25) Hence, several immunotherapeutic approaches against neurodegenerative diseases aim to clear or inhibit the formation of these oligomers or aggregates, which are the key factors behind neurodegeneration.(p1) As will be apparent from the discussion in the following sections, strategies targeting oligomers have shown promise in clinical settings.
[124] Research priorities for neuroimmunology: identifying the key research ... — Neuroimmunology represents a rapidly expanding area of research with a high potential to improve human health, catalysed by increasing evidence implicating the immune system in neurological and psychiatric development and disorders and, conversely, the role of the nervous system in modifying immune function. The authors propose ten questions within four different frameworks: (a) The context of understanding the importance of bidirectional communication (e.g., afferent vs efferent); (b) Deciphering whether neuroimmune crosstalk is more important in some contexts that others (e.g., development vs aging) and the contribution of co-morbidities; (c) The need for advancement and development of newer technologies to non-invasively assess neuroimmune interactions in animals and humans; and (d) The importance of translating answers to these ten fundamental questions into treatments that help patients. Although top-down (efferent) pathways are mentioned, the clear focus of this article is on bottom-up communication from the immune system to the brain, with the aim of improving/understanding/treating mental health disorders.
[125] PDF — W H I T E P A P E R 818-462-8290 | www.sanguinebio.com Overcoming Challenges in Translational Research THE POWER OF BRINGING PATIENTS AND INVESTIGATORS TOGETHER Abstract Translational research emerged as the missing link between basic science and advances in clinical practice meant to markedly improve individual and public health. According to the National Center for Advancing Translational Science, "translation is the process of turning observation in the laboratory, clinic, and community into interventions that improve the health of individuals and the public – from diagnostics and therapeutics to medical procedures and behavioral changes." Stakeholders involved in the process of research translation need to work together to close the gap by increasing collaboration, improving communication, and taking advantage of improvements in the field of biomarkers to promote precision medicine.
[126] From bench to MS bedside: Challenges translating biomarker discovery to ... — An ongoing challenge continues to be translating biomarker discoveries made based on population averages, to clinical decision making at the level of individual patients, for example a measure may, on the average, perform nicely in predicting aggressive disease and poor outcome; however, interpreting a single measure made in an individual
[134] Neuroimmune interactions in health and disease - Springer — The advances of these scientists and many others have provided the foundations for studies on neuroimmune interactions in homeostasis, aging, neurodegeneration, stroke, neuro-HIV, macular degeneration, and other diseases discussed in this issue.
[135] Neuro-immune Interactions in the Tissues - Cell Press — Chiu, Artis, and Chu review the mechanisms underlying the complex interactions between the immune and the nervous systems in different tissues and contexts and argue for the importance of considering infectious and inflammatory disease within a conceptual framework that integrates neuro-immune circuits both local and systemic.
[136] Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell ... — The concept of central nervous system (CNS) inflammation has evolved over the last decades. Neuroinflammation is the response of reactive CNS components to altered homeostasis, regardless of the cause to be endogenous or exogenous. Neurological diseases, whether traumatic, neoplastic, ischemic, metabolic, toxic, infectious, autoimmune, developmental, or degenerative, involve direct and
[137] Neuroimmunology: What It Is & Disorders - Cleveland Clinic — There are several neurological conditions that happen as a result of your immune system attacking healthy parts of your nervous system like multiple sclerosis. What are neuroimmune diseases (neuroimmunological disorders)? Neuroimmune diseases are conditions that affect your brain, spinal cord and nerves (neurological conditions) and happen after your immune system mistakenly attacks part of your nervous system. Each type of neuroimmune condition has different symptoms depending on what part of your nervous system your immune system targets during inflammation. They may work closely with your current care team to find treatment options for complex neuroimmune diseases that affect how your nervous system functions. Neuroimmunologists study neuroimmunology, or the link between your nervous and immune systems.
[140] A Comprehensive Review on Neuroimmunology: Insights from Multiple ... — Articles meeting certain criteria were selected for inclusion: studies or research articles focused on neuroimmunology; publications providing insight into pathophysiology, etiology, clinical aspects, and immunology implications related to multiple sclerosis as they apply to neuroimmunology; clinical trials/experimental/observational research investigating therapeutic developments/interventions regarding MS/related neuroinflammatory conditions; and publications available either in English or with accessible English translations to ensure comprehension. So, MS research highlights the critical role played by immune cell interactions in the development of multiple sclerosis (MS). (a)Uncovering Underlying Mechanisms: Exploring the interrelations between MS’s immune and neurological systems can provide insight into specific physiological and molecular processes driving disease development while pinpointing key immune cell types, cytokines, and chemokines associated with inflammation and demyelination, which will allow targeted therapies;
[141] Neuroimmune interactions in health and disease | Seminars in ... — Moreover, future investigations exploring the gut-immune-brain interactions may provide new insight into CNS inflammatory disease and physiologic processes in the brain. References Nguyen M, Palm NW (2022) Gut instincts in neuroimmunity from the eighteenth to twenty-first centuries.
[142] The Neuro-Immune Axis: Prospect for Novel Treatments for Mental Disorders — The management of these multi-factorial mental disorders needs a new and integrated therapeutic approach, and prospects for novel treatment are as follows: Targeting the neuroinflammatory response in the CNS that disturbs neurotransmitter levels and connectivity, with existing immunomodulatory and anti-inflammatory drugs or/and medical food
[143] Immunoneuropsychiatry — novel perspectives on brain disorders — Immune dysregulation plays a role not only in classical autoimmune brain diseases such as multiple sclerosis and autoimmune encephalitis but also in psychiatric disorders such as schizophrenia, autism spectrum disorder, bipolar disorder and depression. Am. J. Am. J. Am. J. This study shows that peripheral inflammatory stimuli induce differential epigenetic modulation of brain-resident microglia, influencing symptoms in a mouse model of AD; these findings provide a mechanistic link between inflammation, innate immunity and neuropsychiatric disease. Am. J. Am. J. Am. J. Am. J. This study shows that peripheral inflammatory stimuli induce differential epigenetic modulation of brain-resident microglia, influencing symptoms in a mouse model of AD; these findings provide a mechanistic link between inflammation, innate immunity and neuropsychiatric disease. Am. J.
[144] Brain-immune interaction mechanisms: Implications for cognitive ... — The psychiatric disorder of depression in the brain, for example, is closely linked to two‐way communication between the immune system and the brain. 30, 31 Experiments by Kipnis et al. showed that the cognitive abilities of mice were impaired in the absence of mature T cells, but this effect could be restored by passive T‐cell transfer
[145] Neuroimmunology and psychiatric disorders - conpas — Conclusion Neuroimmunology represents a promising frontier in understanding and treating psychiatric disorders. The recognition of the immune system's role in brain function and pathology has significantly shifted the paradigm of mental health research.
[148] Astrocytes: Key Regulators of Neuroinflammation - PubMed — Astrocytes are crucial regulators of innate and adaptive immune responses in the injured central nervous system. Depending on timing and context, astrocyte activity may exacerbate inflammatory reactions and tissue damage, or promote immunosuppression and tissue repair. Recent literature has unveiled …
[149] The semantics of microglia activation: neuroinflammation, homeostasis ... — Altogether these findings show that microglia have dual roles in driving the pathological hallmarks of neuroinflammation and preserving and repairing damaged tissue in stroke . Alzheimer's disease. Numerous studies demonstrate that microglia and neuroinflammation play a role in the pathogenesis of Alzheimer's disease (AD).
[150] Neuroinflammation in neurodegenerative disorders: the roles of ... — Here, we review the roles of inflammatory responses in neurodegenerative diseases, such as AD, PD, and ALS, focusing on the roles of microglia and astrocytes and their relationships. Pro-inflammatory cytokines are debris from pathogens or damaged cells, and they activate the resting microglia to express pro-inflammatory factors such as IL-1β, TNF-α, IL-6, nitric oxide (NO), and proteases, which have detrimental effects in neurodegenerative diseases (Fig. 1, Fig. 2) . Due to the complexity of microglia and astrocyte phenotypes and the various types of drugs, the stages of neurodegenerative diseases (more pro-inflammatory than neuroprotective) and the conditions of patients (confirmed pathology of disease and likely to progress within few years) may be crucial for demonstrating the benefits of anti-inflammatory treatments in clinical trials.
[151] Microglia in neurodegenerative diseases: mechanism and potential ... — This highlights the crucial role of microglia-astrocyte crosstalk in the CNS's response to insults, injuries, or inflammatory stimuli. 110 Microglia have the potential to enhance the
[152] Neuroimmune Connections in Aging and Neurodegenerative Diseases — Normal brain aging and neurodegenerative disease share common pathological hallmarks such as cognitive impairment and loss of brain volume following inflammation. ... Key players in neuroimmune interactions are ... The fact that increased activation of the immune system is linked to a more severe disease progression in HD suggests that the
[172] Neuroimmune interactions in peripheral tissues - Klose - 2021 ... — Neuroimmune interactions have been revealed to be at the centre stage of tissue defence, organ homeostasis, and organismal physiology. Neuronal and immune cell subsets have been shown to colocalize in discrete tissue environments, forming neuroimmune cell units that constitute the basis for bidirectional interactions. ... The role of cytokines
[174] Neuroinflammation: An Integrating Overview of Reactive-Neuroimmune Cell ... — Neuropoietic cytokines are a group of immune mediators that participate in normal brain development, promoting neural precursors' proliferation, fate determination and differentiation, neuronal and glia migration, cell survival, and activity-dependent changes in synaptic function. In response to inflammation challenge, microglia promptly becomes ameboid and upregulates cell surface receptors involved in innate immune responses, proinflammatory type (classical or M1 activation). The pleiotropic inflammatory cytokine TNF-α regulates immune responses, inflammation, proliferation, and cell death (apoptosis and necrosis) and regulates apoptosis binding to its membrane receptor 1 (TNF-R1). In a brain hypoxia-ischemia (H/I) mouse model, the expression of TIM-3 (a member of the T cell immunoglobulin that downregulates the TH1-dependent immune response) increases in activated microglia and astrocytes (brain resident immune cells) depending on HIF-1_α_ .
[175] Neuromodulation by the immune system: a focus on cytokines — Interactions between the immune system and the nervous system have been described mostly in the context of diseases. More recent studies have begun to reveal how certain immune cell-derived soluble effectors, the cytokines, can influence host behaviour even in the absence of infection. In this Revie …
[177] Neuroimmunology: What It Is & Disorders - Cleveland Clinic — There are several neurological conditions that happen as a result of your immune system attacking healthy parts of your nervous system like multiple sclerosis. What are neuroimmune diseases (neuroimmunological disorders)? Neuroimmune diseases are conditions that affect your brain, spinal cord and nerves (neurological conditions) and happen after your immune system mistakenly attacks part of your nervous system. Each type of neuroimmune condition has different symptoms depending on what part of your nervous system your immune system targets during inflammation. They may work closely with your current care team to find treatment options for complex neuroimmune diseases that affect how your nervous system functions. Neuroimmunologists study neuroimmunology, or the link between your nervous and immune systems.
[178] Neuroimmunological Disorders Diagnosis - Atlantic Health — Diagnosis of neuroimmunological disorders requires detailed clinical evaluation and appropriately targeted diagnostic testing, such as neurophysiologic testing, neuro-imaging, blood tests and sometimes cerebrospinal fluid assessment. Treatment usually targets the abnormal immune response, directly addressing the disorder, or can be directed at
[179] Neuroimmunology Diseases - Providence — Treatment for Neuroimmunological Disorders. There are many immune-related conditions that can affect various parts of the central and peripheral nervous system, and symptoms can vary from patient to patient. That's why your care team works closely with you to create a treatment plan based on your specific disorder and unique needs.
[183] Understanding Childhood Neuroimmune Diseases of the Central Nervous ... — A small number of pediatric patients have been included in these reports, and their clinical presentation is characterized by a variable association of symptoms of cognitive, memory, and behavioral impairment and movement disorders, although the most common feature is a refractory/superrefractory status epilepticus (80-83).
[184] Neurologic Manifestations of Common Variable Immunodeficiency — pathways that lead to this defect in patients with CVID are varied. Between 10% and 20% of cases with CVID have been shown to have a heritable cause to date; monogenic forms of CVID account for 2%-10% of patients, and the remainder of cases are polygenic or multifactorial.4 Clinical phenotypes in patients with CVID are highly variable
[185] Advances in gene therapy approaches targeting neuro-inflammation in ... — Advances in gene therapy approaches targeting neuro-inflammation in neurodegenerative diseases - ScienceDirect However, recent advances in gene therapy offer promising avenues for addressing neuroinflammation (Forman et al., 2004). This review aims to explore the latest advancements in gene therapy strategies that target neuroinflammation in neurodegenerative diseases. While the domain of gene therapy for NDs is still in its nascent stages, insights gained from other disorders may be effectively used to enhance the translational capacity of gene therapy for NDs. Although the effective transport of therapeutic DNA into mammalian cells by in vitro methods was established many years ago (Bibi et al., 2023), the in-vivo administration of genetic material has been hindered by many hurdles (Crystal, 2014).
[186] Toward curing neurological autoimmune disorders: Biomarkers ... — This article by Segal et al provides a comprehensive overview of immunopathogenic mechanisms of autoimmune neurological disorders, focusing on the interplay between humoral and cellular immunity, recent therapeutic advancements, and key challenges in targeting immune tolerance breakdown and effector pathways.
[187] Frontiers of Neurodegenerative Disease Treatment: Targeting Immune ... — In brain parenchyma, microglia are the key resident immune cells (Goldmann et al., 2016), and activation of these cells is well documented to be observed in various NDs. In addition, peripheral immune cells can participate in NDs by infiltrating into the brain shaping microglia into a pro-inflammatory phenotype and accelerating disease progression (Gao et al., 2023). During disease conditions, besides resident immune cells such as microglia and infiltrating peripheral immune cells into the brain parenchyma, recent research revealed that the resident immune cells present in the non-parenchymal regions situated at brain borders may play a critical role in maintaining neuronal health, responding to injury, and regulating inflammation within the CNS (Croese et al., 2021, Rustenhoven and Kipnis, 2022, Yshii et al., 2022).
[189] The role of inflammation in neurodegeneration: novel insights into the ... — Even though the exact role of neuroinflammation in neurodegeneration still remains debated, dysregulation of the immune system is a pathological hallmark in nearly all neurodegenerative diseases .
[191] B cells in autoimmune and neurodegenerative central nervous system diseases — B cells are essential components of the adaptive immune system and have important roles in the pathogenesis of several central nervous system (CNS) diseases. Besides producing antibodies, B cells perform other functions, including antigen presentation to T cells, production of proinflammatory cytoki …
[193] The role of regulatory T cells in neurodegenerative diseases — A specific subset of T cells, currently recognized as FOXP3 + CD25 + CD4 + regulatory T cells (Tregs), are pivotal in suppressing autoimmunity and maintaining immune homeostasis by mediating self-tolerance at the periphery as shown in autoimmune diseases and cancers. A growing body of evidence shows that Tregs are not only important for
[194] The immune system in neurological diseases: What innate-like T cells ... — The contribution of T cells to MS disease has been intensely linked to the production of various proinflammatory cytokines, such as IFN-γ and TNF-α. 42 Therefore, T H 1 cells were previously thought for many years to be the central immune cell with a critical pathogenic role in MS. 42 However, much attention has been directed toward γδ T
[195] Multiple Sclerosis & Clinical Neuroimmunology Research Program ... — Comprehensive Care. An interdisciplinary approach is needed to provide the most comprehensive care for MS and other complex neuroimmunological conditions. Our center prioritizes team-based research that finds ways to enhance the delivery of the most comprehensive, patient-centered care for all people with MS and other neuroimmunological disorders.
[196] Neuroimmunology Diseases - Providence — Treatment for Neuroimmunological Disorders. There are many immune-related conditions that can affect various parts of the central and peripheral nervous system, and symptoms can vary from patient to patient. That's why your care team works closely with you to create a treatment plan based on your specific disorder and unique needs.
[200] Identification of Cytochrome P450 2E1 as a Novel Target in ... — Mechanistically, Q11 attenuated microglial activation, neuronal damage, oxidative stress, and neuroinflammation by suppressing the PI3K/Akt, STAT1/3, and NF-κB signaling pathways. These findings establish CYP2E1 as a druggable target for neuroinflammation and propose Q11 as a promising candidate for treating neuroinflammation-related diseases.
[201] Mechanisms and Emerging Regulators of Neuroinflammation: Exploring New ... — Abstract. Neuroinflammation is a complex and dynamic response of the central nervous system (CNS) to injury, infection, and disease. While acute neuroinflammation plays a protective role by facilitating pathogen clearance and tissue repair, chronic and dysregulated inflammation contributes significantly to the progression of neurodegenerative disorders such as Alzheimer's disease, Parkinson
[202] Frontiers of Neurodegenerative Disease Treatment: Targeting Immune ... — In brain parenchyma, microglia are the key resident immune cells (Goldmann et al., 2016), and activation of these cells is well documented to be observed in various NDs. In addition, peripheral immune cells can participate in NDs by infiltrating into the brain shaping microglia into a pro-inflammatory phenotype and accelerating disease progression (Gao et al., 2023). During disease conditions, besides resident immune cells such as microglia and infiltrating peripheral immune cells into the brain parenchyma, recent research revealed that the resident immune cells present in the non-parenchymal regions situated at brain borders may play a critical role in maintaining neuronal health, responding to injury, and regulating inflammation within the CNS (Croese et al., 2021, Rustenhoven and Kipnis, 2022, Yshii et al., 2022).
[212] Immune dysregulation and neurodegenerative diseases — In the last decades, several studies observed an increase of proinflammatory cytokines, such as TNF-α and IL-1β with normal aging .Besides, the adaptive immune system is dysregulated with a reduction of circulating naïve T cells and an accumulation of late stage differentiated memory T cells , .Inflammaging and peripheral immunosenescence promote neuroinflammation, influencing
[214] Peripheral and central neuroimmune mechanisms in Alzheimer's disease ... — The integrity of the blood-brain barrier (BBB) emerges as a crucial factor in AD progression, as its compromise facilitates the infiltration of peripheral immune cells into the central nervous system (CNS), exacerbating neuroinflammation and accelerating cognitive decline . In AD patients, BBB dysfunction facilitates the infiltration of peripheral immune cells, particularly CD8+ T cells, into the CNS, thereby exacerbating neuroinflammation and accelerating disease progression . Therapeutic strategies targeting microglia-CD8+ T-cell interactions, such as microglial or T-cell depletion or the inhibition of IFN-γ signaling, may mitigate tau-mediated neurodegeneration and attenuate AD-associated neuroinflammation and neurodegenerative changes . While B-cell-derived immunoglobulins that target Aβ may impede plaque formation and disease progression, they may concurrently impair microglial function and exacerbate AD pathology .
[217] Research priorities for neuroimmunology: identifying the key research ... — Neuroimmunology represents a rapidly expanding area of research with a high potential to improve human health, catalysed by increasing evidence implicating the immune system in neurological and psychiatric development and disorders and, conversely, the role of the nervous system in modifying immune function. The authors propose ten questions within four different frameworks: (a) The context of understanding the importance of bidirectional communication (e.g., afferent vs efferent); (b) Deciphering whether neuroimmune crosstalk is more important in some contexts that others (e.g., development vs aging) and the contribution of co-morbidities; (c) The need for advancement and development of newer technologies to non-invasively assess neuroimmune interactions in animals and humans; and (d) The importance of translating answers to these ten fundamental questions into treatments that help patients. Although top-down (efferent) pathways are mentioned, the clear focus of this article is on bottom-up communication from the immune system to the brain, with the aim of improving/understanding/treating mental health disorders.
[218] Neuroimmunology: reviews and perspectives on recent advances — The authors nicely point out important gaps in our understanding, particularly with regards to whether and how immune status of the GI tract (or a segment) are represented in higher centers of the brain and whether and how the brain may then use that information to regulate the GI system in a top-down manner. If how immune cells other than macrophages regulate neuronal functions inside the brain is only alluded to in the aforementioned reviews, Kipnis and colleagues put it front and center in their piece .
[219] The immune system and its role in the nervous system — Neuroimmunology research employs endpoint assays derived from immunology, neuroscience, and methods that are standard across diverse fields such as genetics and cellular biology. Again, model systems and assays are selected that represent one or a few aspects of a particular outcome and minimize confounding variables.
[225] Neural immune pathways and their connection to inflammatory diseases — The immune system signals the CNS through immune mediators and cytokines that can cross the blood-brain barrier, or signal indirectly through the vagus nerve or second messengers. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease.
[227] Modulation of the central nervous system immune response and ... — Despite initial protective function, chronic activation of immune cells and persistent inflammation can exacerbate neuronal damage and contribute to disease progression. 10 Wnt signaling pathway is a highly conserved pathway involved in many aspects of development and plays a crucial role in regulating immune responses in the CNS.
[243] Systems neuroimmunology: a review of multiomics methodologies to ... — Compared with traditional methods in neuroimmunology, which study one pathway or gene at a time, emerging multiomics methodologies allow for holistic interrogation of multiple immune-signaling pathways to test hypotheses and the effects of therapeutics at a systems level.
[244] Integrative Methods and Practical Challenges for Single-cell Multi ... — Rather than the traditional single-omics approach of studying biological processes from the genomics or transcriptomics perspective, multi-omics methods allow researchers to explore how two or multiple other realms interact and jointly produce biological observations.
[265] Altered Gut Microbiota Contributes to Acute-Respiratory-Distress ... — Growing evidence suggests that the gut microbiota, known as the "second brain", regulates neuroinflammation through the microbiota-gut-brain axis, impacting the host's immune system and behaviors [11 - 14].
[267] The Role of Gut Microbiota in Neurodegenerative Diseases: Current ... — A paradigm change in therapy strategies and new avenues for future study have been made possible by the complex interactions between gut microbiota and neurodegenerative disorders. Utilizing the gut-brain axis's two-way connection offers new ways to slow disease progression, enhance patient outcomes, and even change how neurodegenerative
[268] Role of Gut Microbiota in Neurological Disorders and Its Therapeutic ... — Keywords: gut microbiota, neurological disorders, pathogenesis, therapy, gut-brain axis. 1. Introduction ... To further develop therapeutic strategies, it is necessary to establish the effects of food components and metabolites generated by microbes on host physiology and health . Our previous studies on yoga and meditation and yoga
[274] Neuroinflammation as a therapeutic target in neurodegenerative diseases ... — A major challenge in the development of treatment strategies for most progressive neurodegenerative diseases is their complex multifactorial etiology and heterogeneous disease course , , . For the most common neurodegenerative diseases, such as AD, PD, and amyotrophic lateral sclerosis (ALS), the precise causes of disease onset and
[275] Will cellular immunotherapies end neurodegenerative diseases? - Cell Press — Neurodegenerative disorders present major challenges to global health, exacerbated by an aging population and the absence of therapies. Despite diverse pathological manifestations, they share a common hallmark, loosely termed 'neuroinflammation'. The prevailing dogma is that the immune system is an active contributor to neurodegeneration; however, recent evidence challenges this. By
[276] Toward curing neurological autoimmune disorders: Biomarkers ... — A major challenge in therapeutically targeting B cells is that current therapies are largely infused, hence, may not effectively distribute to essential driving immune compartments removed from the bloodstream. 119 Thus, there is great need to identify the key immunological niches driving human disease to deliver compartment-specific therapeutics.
[277] Immunotherapies for Neurodegenerative Diseases - PMC — Herein, passive immunization of FTD/ALS C9-BAC transgenic mice with anti-GA RAN antibodies, α-GA1, α-GP1, and α-GA2, has effectively reduced neuroinflammation and neurodegeneration in the anterior and posterior horns of the lumbar spine (209). | Immune (169) | ACI-24 | Alzheimer's disease | Aggregated Aβ peptides | Phase II: 2018-000445-39 | Safe and tolerated | Clinical development of aducanumab, an anti-Aβ human monoclonal antibody being investigated for the treatment of early alzheimer's disease. Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer's disease: randomised, double-blind, placebo-controlled, first-in-human study. Safety, tolerability and immunogenicity of an active anti-Aβ 40 vaccine (ABvac40) in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase I trial. Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease.
[285] Journal of Clinical Neurology and Neurosurgery — Ethical and societal implications of neuroinflammation research are considered. This article concludes by emphasizing the importance of interdisciplinary collaboration and the promising prospects for understanding and managing neuroinflammatory conditions.
[286] The Case for Understanding Interdisciplinary Relationships in Health ... — Another example of interdisciplinary collaboration is accountable care organizations that mandate interdisciplinary relationships in the form of teams consisting of a primary care physician, nursing staff, and specialists who care for patients.10,11 This kind of health care collaboration has been suggested as an effective option for lowering the cost of patient care and improving patient outcomes.10 Kaufman et al reviewed 42 articles that assessed the effect of accountable care organizations on health care utilization, processes of care, and outcomes.12 The articles included in the review were 24 Medicare studies, 5 Medicaid studies, and 13 private payer studies.
[287] The Importance of Interdisciplinary Collaboration in Research — The complex issues related to multisystem syndromes are more appropriately addressed when an interdisciplinary approach is used. A cardiologist might notice a cardiovascular manifestation of an autoimmune disease that also occurs in neurology.
[288] Pioneering discovery and therapeutics at the brain-vascular-immune ... — In the coming decade, scientific breakthroughs at the blood-brain-immune interface will emerge from interdisciplinary collaborative networks of immunologists, neuroscientists, hematologists, geneticists, computer scientists, physicists, bioengineers, drug developers, and clinical researchers.