scholarly journals The Impact of β-1,4-Galactosyltransferase V on Microglial Function

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiaoyu Wang ◽  
Naiqi Shi ◽  
Meiqi Hui ◽  
Hui Jin ◽  
Shumei Gao ◽  
...  
Keyword(s):  
Immune Cells ◽  
Biological Function ◽  
Tumor Necrosis Factor Receptor ◽  
Vital Role ◽  
Inflammatory Factors ◽  
Spatial Learning And Memory ◽  
The Central Nervous System ◽  
Microglial Migration ◽  
The Impact ◽  
Necrosis Factor

β-1,4 Galactosyltransferase V (β-1,4-GalT V) belongs to the β-1,4 galactosyltransferase family, which modifies proteins and plays a vital role in biological function. Our previous study revealed that β-1,4-GalT V was expressed in the cortex and hippocampus and participated in the recovery of spatial learning and memory in rats with traumatic brain injury. However, the expression of β-1,4-GalT V in microglia, resident immune cells in the central nervous system, and its impact on microglia in resting and lipopolysaccharide-triggered activated stages are elusive. In this study, we clarified that β-1,4-GalT V expresses in microglia, and it regulates microglial migration, proliferation, and release of the inflammatory factors. We also observed that β-1,4-GalT V affects the expression level of tumor necrosis factor receptor (TNFR)2 instead of TNFR1. These results strongly support the fact that β-1,4-GalT V is involved in microglial function.

scholarly journals Extracellular Vesicle as a Source of Alzheimer’s Biomarkers: Opportunities and Challenges

2019 ◽  
Vol 20 (7) ◽  
pp. 1728 ◽  
Author(s):  
Seongju Lee ◽  
Sakulrat Mankhong ◽  
Ju-Hee Kang
Keyword(s):  
Clinical Evidence ◽  
Biological Function ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Vital Role ◽  
Synaptic Loss ◽  
Memory Decline ◽  
Disease Propagation ◽  
The Central Nervous System ◽  
Yield And Purity

Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease characterized by memory decline and cognitive dysfunction. Although the primary causes of AD are not clear, it is widely accepted that the accumulation of amyloid beta (Aβ) and consecutive hyper-phosphorylation of tau, synaptic loss, oxidative stress and neuronal death might play a vital role in AD pathogenesis. Recently, it has been widely suggested that extracellular vesicles (EVs), which are released from virtually all cell types, are a mediator in regulating AD pathogenesis. Clinical evidence for the diagnostic performance of EV-associated biomarkers, particularly exosome biomarkers in the blood, is also emerging. In this review, we briefly introduce the biological function of EVs in the central nervous system and discuss the roles of EVs in AD pathogenesis. In particular, the roles of EVs associated with autophagy and lysosomal degradation systems in AD proteinopathy and in disease propagation are discussed. Next, we summarize candidates for biochemical AD biomarkers in EVs, including proteins and miRNAs. The accumulating data brings hope that the application of EVs will be helpful for early diagnostics and the identification of new therapeutic targets for AD. However, at the same time, there are several challenges in developing valid EV biomarkers. We highlight considerations for the development of AD biomarkers from circulating EVs, which includes the standardization of pre-analytical sources of variability, yield and purity of isolated EVs and quantification of EV biomarkers. The development of valid EV AD biomarkers may be facilitated by collaboration between investigators and the industry.

scholarly journals The Impact of IgA and the Microbiota on CNS Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Annie Pu ◽  
Dennis S. W. Lee ◽  
Baweleta Isho ◽  
Ikbel Naouar ◽  
Jennifer L. Gommerman
Keyword(s):  
Immune Cells ◽  
Preclinical Models ◽  
Potential Therapeutic Target ◽  
Cns Disease ◽  
Mechanistic Insight ◽  
Circulating Lymphocytes ◽  
The Central Nervous System ◽  
Peripheral Immune Cells ◽  
The Impact ◽  
Insight Into

Although anatomically distant from the central nervous system (CNS), gut-derived signals can dynamically regulate both peripheral immune cells and CNS-resident glial cells to modulate disease. Recent discoveries of specific microbial taxa and microbial derived metabolites that modulate neuroinflammation and neurodegeneration have provided mechanistic insight into how the gut may modulate the CNS. Furthermore, the participation of the gut in regulation of peripheral and CNS immune activity introduces a potential therapeutic target. This review addresses emerging literature on how the microbiome can affect glia and circulating lymphocytes in preclinical models of human CNS disease. Critically, this review also discusses how the host may in turn influence the microbiome, and how this may impact CNS homeostasis and disease, potentially through the production of IgA.

scholarly journals ATVB Distinguished Scientist Award

2017 ◽  
Vol 37 (5) ◽  
pp. 764-777 ◽  
Author(s):  
Klaus Ley ◽  
Norbert Gerdes ◽  
Holger Winkels
Keyword(s):  
Immune Cells ◽  
Tumor Necrosis ◽  
Critical Role ◽  
Tumor Necrosis Factor Receptor ◽  
Major Effect ◽  
Therapeutic Approaches ◽  
Cell Responses ◽  
Genetic Deletion ◽  
Antigen Presenting ◽  
Necrosis Factor

Objective— Immune cells play a critical role in atherosclerosis. Costimulatory and coinhibitory molecules of the tumor necrosis factor receptor and CD28 immunoglobulin superfamilies not only shape T-cell and B-cell responses but also have a major effect on antigen-presenting cells and nonimmune cells. Approach and Results— Pharmacological inhibition or activation of costimulatory and coinhibitory molecules and genetic deletion demonstrated their involvement in atherosclerosis. This review highlights recent advances in understanding how costimulatory and coinhibitory pathways shape the immune response in atherosclerosis. Conclusions— Insights gained from costimulatory and coinhibitory molecule function in atherosclerosis may inform future therapeutic approaches.

Neuroimmune interactions and pain during postnatal development

2013 ◽  
pp. 65-73
Author(s):  
David Vega-Avelaira ◽  
Simon Beggs
Keyword(s):  
Postnatal Development ◽  
Immune Cells ◽  
Defensive Responses ◽  
Nociceptive Pathways ◽  
Neuroimmune Interactions ◽  
The Central Nervous System ◽  
And Function ◽  
Type Of Injury ◽  
The Impact ◽  
Role And Function

The immune system is essential for identifying and mounting defensive responses to tissue damage and infection. In addition, it is increasingly recognized that interactions between immune cells and nociceptive pathways can modulate pain sensitivity. The role and function of immune cells in the central nervous system changes during postnatal development, and as a result, the impact of neuroimmune interactions on pain signalling varies with both age and the type of injury.

scholarly journals Different Activation of TRAF4 and TRAF6 in Inflammatory Bowel Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Shen ◽  
Yuqi Qiao ◽  
Zhihua Ran ◽  
Tianrong Wang
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Cells ◽  
Bowel Disease ◽  
Binding Sites ◽  
Tumor Necrosis ◽  
Expression Patterns ◽  
Tumor Necrosis Factor Receptor ◽  
Inflammatory Bowel ◽  
Necrosis Factor ◽  
Comprehensive Study

In recent years, interests combining the exploration of tumor necrosis factor receptor-associated factor 4 (TRAF4) and TRAF6 in immune cells and transgenic mice are emerging. Although it has been found that TRAF4 and TRAF6 share the same TRAF binding sites, comprehensive study of TRAF4 and TRAF6 in inflammatory bowel disease (IBD) is still lacking. This paper shows similar and different expression patterns of TRAF4 and TRAF6 in patients with IBD. The results indicate that TRAF4 and TRAF6 are overexpressed in IBD. TRAF4 and TRAF6 play different roles in the pathogenesis of IBD. Moreover, TRAF4 may be an indicator of endoscopic disease activity of UC and TRAF6 preactivation can be detected in noninflamed colonic segments.

scholarly journals Immune Checkpoint Expression on Immune Cells of HNSCC Patients and Modulation by Chemo- and Immunotherapy

2020 ◽  
Vol 21 (15) ◽  
pp. 5181
Author(s):  
Lisa K. Puntigam ◽  
Sandra S. Jeske ◽  
Marlies Götz ◽  
Jochen Greiner ◽  
Simon Laban ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Immune Checkpoints ◽  
Healthy Donors ◽  
Necrosis Factor

Endogenous control mechanisms, including immune checkpoints and immunosuppressive cells, are exploited in the process of tumorigenesis to weaken the anti-tumor immune response. Cancer treatment by chemotherapy or immune checkpoint inhibition can lead to changes of checkpoint expression, which influences therapy success. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) were isolated from head and neck squamous cell carcinoma (HNSCC) patients (n = 23) and compared to healthy donors (n = 23). Immune checkpoint expression (programmed cell death ligand 1 (PD-1), tumor necrosis factor receptor (TNFR)-related (GITR), CD137, tumor necrosis factor receptor superfamily member 4 (TNFRSF4) (OX40), t-cell immunoglobulin and mucin-domain containing-3 (TIM3), B- and T-lymphocyte attenuator (BTLA), lymphocyte-activation gene 3 (LAG3)) was determined on immune cells by flow cytometry. PD-L1 expression was detected on tumor tissue by immunohistochemistry. Immune cells were treated with immuno- and chemotherapeutics to investigate treatment-specific change in immune checkpoint expression, in vitro. Specific changes of immune checkpoint expression were identified on PBL and TIL of HNSCC patients compared to healthy donors. Various chemotherapeutics acted differently on the expression of immune checkpoints. Changes of checkpoint expression were significantly less pronounced on regulatory T cells compared to other lymphocyte populations. Nivolumab treatment significantly reduced the receptor PD-1 on all analyzed T cell populations, in vitro. The specific immune checkpoint expression patterns in HNSCC patients and the investigated effects of immunomodulatory agents may improve the development and efficacy of targeted immunotherapy.

scholarly journals Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters

2020 ◽  
Author(s):  
Bertrand Bryche ◽  
Audrey St Albin ◽  
Severine Murri ◽  
Sandra Lacôte ◽  
Coralie Pulido ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lamina Propria ◽  
Olfactory Epithelium ◽  
Immune Cells ◽  
Olfactory Neurons ◽  
Syrian Hamsters ◽  
Sustentacular Cells ◽  
The Central Nervous System ◽  
The Impact

AbstractAnosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-COV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs. We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria.

scholarly journals Dexmedetomidine Inhibits Nlrp3 Inflammasome Priming in BV-2 microglia through the NF-κB Pathway and the ROS-Nlrp3-IL-1β Signaling Axis

2021 ◽  
Author(s):  
Jiawei Xie ◽  
Li Chen ◽  
Yuling Luo ◽  
Jianling Li ◽  
Xianxue Wang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Factors ◽  
Pyrrolidine Dithiocarbamate ◽  
Neurocognitive Dysfunction ◽  
Pyrin Domain ◽  
Tnf Α ◽  
Signaling Axis ◽  
The Impact ◽  
Necrosis Factor ◽  
Receptor Family

Abstract In the brain, the NOD-like receptor family pyrin domain containing 3 (Nlrp3) inflammasome is mostly expressed in microglia and is considered to be the primary cause of perioperative neurocognitive dysfunction (PND). Dexmedetomidine (Dex), a novel kind of clinical anesthetic with anti-inflammatory properties, has been shown to be effective in preventing PND in surgical patients. However, the mechanism of its anti-neuroinflammatory activity is still quite unclear. We examined the impact of Dex administration on Nlrp3 priming in activated BV-2 cells in this research. To investigate the mechanism by which Dex impacts Nlrp3 priming, we employed the inhibitors pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC) to block the NF-κB p65 and the reactive oxygen species (ROS)-Nlrp3-interleukin (IL)-1β signaling axis, respectively. The results showed that Dex substantially decreased the expression of Nlrp3 and p65 and significantly inhibited the levels of the inflammatory factors IL-1β and tumor necrosis factor (TNF)-α in BV-2 cells stimulated with lipopolysaccharide (LPS). Additionally, when the NF-κB pathway was inhibited by PDTC, Dex could aggravate the downregulation of Nlrp3 and IL-1β in BV-2 cells. What is more, Dex negatively regulated the expression of Nlrp3 and IL-1β in activated BV-2 cells when NAC was added. These results showed that Dex inhibited Nlrp3 priming in LPS-induced BV-2 cells, presumably via blocking the NF-κB pathway and the ROS-Nlrp3-IL-1β signaling axis.

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