Neuroinflammation and Neurodegenerative Diseases

2016 ◽  
Author(s):  
Taylor R. Jay ◽  
Shane M. Bemiller ◽  
Lee E. Neilson ◽  
Paul J. Cheng-Hathaway ◽  
Bruce T. Lamb
Keyword(s):  
Neurodegenerative Diseases ◽  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Active Role ◽  
Immune Cell Activation ◽  
Excitotoxic Damage ◽  
And Function ◽  
Inflammatory Molecules ◽  
The Brain

Neuroinflammation has long been associated with many neurodegenerative diseases (NDDs). Immune-related genetic and environmental risk factors have recently been identified for NDDs, suggesting that neuroinflammation can play an active role in modifying NDD pathologies. Immune cells that underlie this neuroinflammatory response can have both beneficial and detrimental roles in NDDs. These cells can engage in clearance of debris and provide important survival factors to neighboring neurons. However, these cells can also release inflammatory molecules that promote oxidative stress and excitotoxic damage in surrounding neurons, and aberrantly clear healthy cells and structures from the brain. In turn, the cells within the brain play important roles in determining the phenotype and function of these immune cells, and changes in the interaction among these cells in the context of disease can lead to detrimental immune cell activation. There has been recent interest in developing inflammation-related biomarkers to help diagnose NDDs and immune-targeted therapeutics.

scholarly journals Carbohydrate and Amino Acid Metabolism as Hallmarks for Innate Immune Cell Activation and Function

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 562 ◽  
Author(s):  
Haoxin Zhao ◽  
Lydia N. Raines ◽  
Stanley Ching-Cheng Huang
Keyword(s):  
Amino Acids ◽  
Immune Cells ◽  
Amino Acid Metabolism ◽  
Cell Activation ◽  
Acid Metabolism ◽  
Immune Cell ◽  
Innate Immune ◽  
Effector Functions ◽  
Immune Cell Activation ◽  
And Function

Immune activation is now understood to be fundamentally linked to intrinsic and/or extrinsic metabolic processes which are essential for immune cells to survive, proliferate, and perform their effector functions. Moreover, disruption or dysregulation of these pathways can result in detrimental outcomes and underly a number of pathologies in both communicable and non-communicable diseases. In this review, we discuss how the metabolism of carbohydrates and amino acids in particular can modulate innate immunity and how perturbations in these pathways can result in failure of these immune cells to properly function or induce unfavorable phenotypes.

scholarly journals Neuroimmune Semaphorin 4A in Cancer Angiogenesis and Inflammation: A Promoter or a Suppressor?

2018 ◽  
Vol 20 (1) ◽  
pp. 124 ◽  
Author(s):  
Apoorva Iyer ◽  
Svetlana Chapoval
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Fine Tuning ◽  
Breast Cancers ◽  
Immune Functions ◽  
Immune Cell Activation ◽  
Important Regulator ◽  
And Function ◽  
Axon Guidance Molecule ◽  
Guidance Molecule

Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function, instructing a fine tuning of the immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal, and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro- or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.

scholarly journals Immunomodulation of Epithelium

1996 ◽  
Vol 10 (4) ◽  
pp. 243-248 ◽  
Author(s):  
Mary H Perdue
Keyword(s):  
Mast Cell ◽  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Regulatory System ◽  
Mast Cell Activation ◽  
Immune Cell Activation ◽  
Inflammatory Conditions ◽  
Close Proximity ◽  
Antigenic Material

Many studies have provided evidence that the immune system is a key regulatory system of intestinal function. The interaction of immune cells with the gut epithelium plays an important role in host defence, acting to eliminate pathogens, antigens and other noxious material from the lumen of the gastrointestinal tract. During inflammatory conditions of the gut, the mucosa becomes packed with immune cells in close proximity to the enterocytes. Mediators released from these cells have profound effects on epithelial functions. The two main functions of the intestinal epithelium are to transport nutrients, ions and water, and to act as a barrier to prevent unimpeded uptake of antigenic material and microbes from the lumen. Both these functions are altered by immune reactions in response to various stimuli. Topics discussed include mast cells and epithelial function; mast cell-nerve interaction; mast cell activation; neutrophils, eosinophils and macrophages; T cells; and prostaglandins and immune cell activation.

Integrative immunophysiology in the intestinal mucosa

1994 ◽  
Vol 267 (2) ◽  
pp. G151-G165 ◽  
Author(s):  
M. H. Perdue ◽  
D. M. McKay
Keyword(s):  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Intestinal Epithelial ◽  
Immune Cell Activation ◽  
Current State ◽  
Enteric Nerves ◽  
Host Defense Response ◽  
Acid Metabolites ◽  
Epithelial Physiology

Over the past ten years, it has become evident that intestinal epithelial functions such as ion secretion are a host defense response to the presence of antigens, microbes, and other noxious substances in the gut lumen. Such responses are mediated by the activation of immune cells in the mucosa causing release of chemical mediators that act directly or indirectly on the epithelium. Frequently, immune cell products stimulate enteric nerves resulting in amplification. Thus immune cells and nerves form interactive units that can recognize various stimuli both specifically and nonspecifically and initiate mechanisms to eliminate offending material. Here, we review the current state of knowledge regarding immune regulation of epithelial physiology with particular emphasis on the ability of immune cells and their products (biogenic amines, cytokines, arachidonic acid metabolites, oxidants) to alter electrolyte transport. The mast cell will be highlighted in this scheme as this cell has been, and continues to be, the focus of extensive research efforts. However, recently it has become apparent that cells such as lymphocytes, macrophages, and polymorphonuclear leukocytes also play important roles in immunophysiology. The effect of immune cell activation on epithelial functions other than transport, such as permeability, proliferation, and antigen presentation, will be described where appropriate. Finally, we will present evidence that the enterocyte can express an "activated" phenotype and thus participate directly in mucosal immune responses.

scholarly journals Diabetes Prevention by Immunomodulatory FTY720 Treatment in the LEW.1AR1-iddm Rat Despite Immune Cell Activation

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 3555-3565 ◽  
Author(s):  
Anne Jörns ◽  
Klaus Jan Rath ◽  
Taivankhuu Terbish ◽  
Tanja Arndt ◽  
Andreas Meyer zu Vilsendorf ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Diabetes Prevention ◽  
Cell Activation ◽  
Immune Cell ◽  
Spontaneous Diabetes ◽  
Immune Cell Activation ◽  
Gene And Protein Expression ◽  
Draining Lymph Nodes

The prevention of diabetes by the immunomodulatory agent FTY720 (fingolimod) was studied in the LEW.1AR1-iddm (IDDM) rat, an animal model of human type 1 diabetes. Immune cell subtypes and cytokine profiles in pancreatic islets, secondary lymphoid tissue, and serum were analyzed for signs of immune cell activation. Animals were treated with FTY720 (1 mg/kg body weight) for 40 d starting on d 50 of life. Changes in gene and protein expression of cytokines, CD8 markers, monocyte chemoattractant protein-1, inducible NO synthase, and caspase 3 were evaluated. Treatment with FTY720 prevented diabetes manifestation and islet infiltration around d 60 of life, the usual time of spontaneous diabetes development. On d 120, 30 d after the end of FTY720 therapy, diabetes prevention persisted. However, six of 12 treated animals showed increased gene expression of IL-1β, TNF-α, and CD8 markers in pancreas-draining lymph nodes, indicating immune cell activation. In parallel, serum concentrations of these proinflammatory cytokines were increased. These six animals also showed macrophage infiltration without proinflammatory cytokine expression in a small minority (2–3%) of islets. Interestingly, regulatory T lymphocytes were significantly increased in the efferent vessels of the pancreas-draining lymph nodes only in animals without signs of immune cell activation but not in the rats with immune cell activation. This provides an indication for a lack of protective capacity in the animals with activated immune cells. Thus, FTY720 treatment prevented the manifestation of diabetes by promoting the retention of activated immune cells in the lymph nodes, thereby avoiding islet infiltration and β-cell destruction by proinflammatory cytokines.

Biology of the Heparanase–Heparan Sulfate Axis and Its Role in Disease Pathogenesis

2021 ◽  
Vol 47 (03) ◽  
pp. 240-253 ◽  
Author(s):  
Israel Vlodavsky ◽  
Uri Barash ◽  
Hien M. Nguyen ◽  
Shi-Ming Yang ◽  
Neta Ilan
Keyword(s):  
Cell Proliferation ◽  
Heparan Sulfate ◽  
Cell Activation ◽  
Immune Cell ◽  
Enzyme Activation ◽  
Cell Of Origin ◽  
Immune Cell Activation ◽  
Cytokines And Chemokines ◽  
And Function ◽  
Multiple Signaling

AbstractCell surface proteoglycans are important constituents of the glycocalyx and participate in cell–cell and cell–extracellular matrix (ECM) interactions, enzyme activation and inhibition, and multiple signaling routes, thereby regulating cell proliferation, survival, adhesion, migration, and differentiation. Heparanase, the sole mammalian heparan sulfate degrading endoglycosidase, acts as an “activator” of HS proteoglycans, thus regulating tissue hemostasis. Heparanase is a multifaceted enzyme that together with heparan sulfate, primarily syndecan-1, drives signal transduction, immune cell activation, exosome formation, autophagy, and gene transcription via enzymatic and nonenzymatic activities. An important feature is the ability of heparanase to stimulate syndecan-1 shedding, thereby impacting cell behavior both locally and distally from its cell of origin. Heparanase releases a myriad of HS-bound growth factors, cytokines, and chemokines that are sequestered by heparan sulfate in the glycocalyx and ECM. Collectively, the heparan sulfate–heparanase axis plays pivotal roles in creating a permissive environment for cell proliferation, differentiation, and function, often resulting in the pathogenesis of diseases such as cancer, inflammation, endotheliitis, kidney dysfunction, tissue fibrosis, and viral infection.

scholarly journals Metabolic substrate utilization in stress-induced immune cells

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Xiaomin Zhang ◽  
Fabian Zink ◽  
Felix Hezel ◽  
Josef Vogt ◽  
Ulrich Wachter ◽  
...  
Keyword(s):  
Immune Cells ◽  
Metabolic Pathways ◽  
Cell Activation ◽  
Immune Cell ◽  
Tca Cycle ◽  
Therapeutic Interventions ◽  
Functional Changes ◽  
Cell Functions ◽  
Immune Cell Activation ◽  
Metabolic Functions

AbstractImmune cell activation leads to the acquisition of new functions, such as proliferation, chemotaxis, and cytokine production. These functional changes require continuous metabolic adaption in order to sustain ATP homeostasis for sufficient host defense. The bioenergetic demands are usually met by the interconnected metabolic pathways glycolysis, TCA cycle, and oxidative phosphorylation. Apart from glucose, other sources, such as fatty acids and glutamine, are able to fuel the TCA cycle.Rising evidence has shown that cellular metabolism has a direct effect on the regulation of immune cell functions. Thus, quiescent immune cells maintain a basal metabolic state, which shifts to an accelerated metabolic level upon immune cell activation in order to promote key effector functions.This review article summarizes distinct metabolic signatures of key immune cell subsets from quiescence to activation and demonstrates a methodical concept of how to assess cellular metabolic pathways. It further discusses why metabolic functions are of rising interest for translational research and how they can be affected by the underlying pathophysiological condition and/or therapeutic interventions.

scholarly journals Neuroimmune Semaphorin 4A in Cancer Angiogenesis and Inflammation

2018 ◽  
Author(s):  
Apoorva Iyer ◽  
Svetlana P. Chapoval
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Fine Tuning ◽  
Breast Cancers ◽  
Immune Functions ◽  
Immune Cell Activation ◽  
Important Regulator ◽  
And Function ◽  
Axon Guidance Molecule ◽  
Guidance Molecule

Neuroimmune semaphorin 4A (Sema4A), a member of semaphorin family of transmembrane and secreted proteins, is an important regulator of neuronal and immune functions. In the nervous system, Sema4A primarily regulates the functional activity of neurons serving as an axon guidance molecule. In the immune system, Sema4A regulates immune cell activation and function granting a fine tuning of immune response. Recent studies have shown a dysregulation of Sema4A expression in several types of cancer such as hepatocellular carcinoma, colorectal and breast cancers. Cancers have been associated with abnormal angiogenesis. The function of Sema4A in angiogenesis and cancer is not defined. Recent studies have demonstrated Sema4A expression and function in endothelial cells. However, the results of these studies are controversial as they report either pro – or anti-angiogenic Sema4A effects depending on the experimental settings. In this mini-review, we discuss these findings as well as our data on Sema4A regulation of inflammation and angiogenesis, which both are important pathologic processes underlining tumorigenesis and tumor metastasis. Understanding the role of Sema4A in those processes may guide the development of improved therapeutic treatments for cancer.

Modulation of innate immune cell activation and function by Polysaccharide Krestin (PSK)

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
CA Wenner ◽  
H Wang ◽  
A Hill-Force ◽  
MR Martzen ◽  
MR Verneris
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Immune Cell Activation ◽  
And Function

scholarly journals Amino acids: key sources for immunometabolites and immunotransmitters

2020 ◽  
Vol 32 (7) ◽  
pp. 435-446 ◽  
Author(s):  
Michio Miyajima
Keyword(s):  
Amino Acids ◽  
Immune Cells ◽  
Nicotinamide Adenine Dinucleotide ◽  
Cell Activation ◽  
Immune Cell ◽  
Nerve Cells ◽  
Metabolic Reprogramming ◽  
Functional Plasticity ◽  
Immune Cell Activation ◽  
Oxide Synthase

Abstract Immune-cell activation and functional plasticity are closely linked to metabolic reprogramming that is required to supply the energy and substrates for such dynamic transformations. During such processes, immune cells metabolize many kinds of molecules including nucleic acids, sugars and lipids, which is called immunometabolism. This review will mainly focus on amino acids and their derivatives among such metabolites and describe the functions of these molecules in the immune system. Although amino acids are essential for, and well known as, substrates for protein synthesis, they are also metabolized as energy sources and as substrates for functional catabolites. For example, glutamine is metabolized to produce energy through glutaminolysis and tryptophan is consumed to supply nicotinamide adenine dinucleotide, whereas arginine is metabolized to produce nitric acid and polyamine by nitric oxide synthase and arginase, respectively. In addition, serine is catabolized to produce nucleotides and to induce methylation reactions. Furthermore, in addition to their intracellular functions, amino acids and their derivatives are secreted and have extracellular functions as immunotransmitters. Many amino acids and their derivatives have been classified as neurotransmitters and their functions are clear as transmitters between nerve cells, or between nerve cells and immune cells, functioning as immunotransmitters. Thus, this review will describe the intracellular and external functions of amino acid from the perspective of immunometabolism and immunotransmission.

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