Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ILC3, a Central Innate Immune Component of the Gut-Brain Axis in Multiple Sclerosis.

ABSTRACT: Gut immune cells have been increasingly appreciated as important players in the central nervous system (CNS) autoimmunity in animal models of multiple sclerosis (MS). Among the gut immune cells, innate lymphoid cell type 3 (ILC3) is of special interest in MS research, as they represent the innate cell counterpart of the major pathogenic cell population in MS, i.e. T helper (Th)17 cells. Importantly, these cells have been shown to stimulate regulatory T cells (Treg) and to counteract pathogenic Th17 cells in animal models of autoimmune diseases. Besides, they are also well known for their ability to stabilize the intestinal barrier and to shape the immune response to the gut microbiota. Thus, proper maintenance of the intestinal barrier and the establishment of the regulatory milieu in the gut performed by ILC3 may prevent activation of CNS antigen-specific Th17 cells by the molecular mimicry. Recent findings on the role of ILC3 in the gut-CNS axis and their relevance for MS pathogenesis will be discussed in this paper. Possibilities of ILC3 functional modulation for the benefit of MS patients will be addressed, as well.

SUBMITTER: Miljkovic Đ

PROVIDER: S-EPMC8071931 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

The Gut-Brain Axis as a Therapeutic Target in Multiple Sclerosis.

Project description:The CNS is very susceptible to oxidative stress; the gut microbiota plays an important role as a trigger of oxidative damage that promotes mitochondrial dysfunction, neuroinflammation, and neurodegeneration. In the current review, we discuss recent findings on oxidative-stress-related inflammation mediated by the gut-brain axis in multiple sclerosis (MS). Growing evidence suggests targeting gut microbiota can be a promising strategy for MS management. Intricate interaction between multiple factors leads to increased intra- and inter-individual heterogeneity, frequently painting a different picture in vivo from that obtained under controlled conditions. Following an evidence-based approach, all proposed interventions should be validated in clinical trials with cohorts large enough to reach significance. Our review summarizes existing clinical trials focused on identifying suitable interventions, the suitable combinations, and appropriate timings to target microbiota-related oxidative stress. Most studies assessed relapsing-remitting MS (RRMS); only a few studies with very limited cohorts were carried out in other MS stages (e.g., secondary progressive MS-SPMS). Future trials must consider an extended time frame, perhaps starting with the perinatal period and lasting until the young adult period, aiming to capture as many complex intersystem interactions as possible.

| S-EPMC10378521 | biostudies-literature

Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome.

Project description:The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.

| S-EPMC6175760 | biostudies-other

The Gut-CNS Axis in Multiple Sclerosis.

Project description:Multiple sclerosis (MS) is an autoimmune inflammatory disease of the CNS driven by the inflammatory activity of peripheral immune cells recruited to the CNS and by CNS-resident glial cells. MS pathogenesis has been linked to both genetic and environmental factors. In addition, the commensal flora have been shown to modulate immune processes relevant to MS pathogenesis. We discuss the effects of the gut microbiota on T cells and glial cells, and their relevance for the control of inflammation and neurodegeneration in MS. A better understanding of the gut-CNS axis will shed new light on the mechanisms of disease pathogenesis, and may help to guide the development of efficacious therapies for MS.

| S-EPMC8284847 | biostudies-literature

Alemtuzumab treatment alters circulating innate immune cells in multiple sclerosis.

Project description:ObjectiveTo characterize changes in myeloid and lymphoid innate immune cells in patients with relapsing-remitting multiple sclerosis (MS) during a 6-month follow-up after alemtuzumab treatment.MethodsCirculating innate immune cells including myeloid cells and innate lymphoid cells (ILCs) were analyzed before and 6 and 12 months after onset of alemtuzumab treatment. Furthermore, a potential effect on granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-23 production by myeloid cells and natural killer (NK) cell cytolytic activity was determined.ResultsIn comparison to CD4+ T lymphocytes, myeloid and lymphoid innate cell subsets of patients with MS expressed significantly lower amounts of CD52 on their cell surface. Six months after CD52 depletion, numbers of circulating plasmacytoid dendritic cells (DCs) and conventional DCs were reduced compared to baseline. GM-CSF and IL-23 production in DCs remained unchanged. Within the ILC compartment, the subset of CD56bright NK cells specifically expanded under alemtuzumab treatment, but their cytolytic activity did not change.ConclusionsOur findings demonstrate that 6 months after alemtuzumab treatment, specific DC subsets are reduced, while CD56bright NK cells expanded in patients with MS. Thus, alemtuzumab specifically restricts the DC compartment and expands the CD56bright NK cell subset with potential immunoregulatory properties in MS. We suggest that remodeling of the innate immune compartment may promote long-term efficacy of alemtuzumab and preserve immunocompetence in patients with MS.

| S-EPMC5063395 | biostudies-literature

In-silico characterization of GABAT protein found in gut-brain axis associated bacteria of healthy individuals and multiple sclerosis patients.

Project description:BackgroundMultiple sclerosis (MS) is a neurodegenerative disease characterized by inflammation and demyelination of neurons. There is evidence to suggest that level of a neurotransmitter gamma-aminobutyric acid (GABA), due to the degradation by γ-aminobutyric acid transaminase (GABAT), is reduced in certain areas of the brain in MS patients. MS is always accompanied by gut bacteria dysbiosis. In healthy individuals, Faecalibacterium sp. while in MS patients A. calcoaceticus, Clostridium sp. and S. typhimurium are found abundantly. Although all these microbes produce GABAT but only in MS patients this enzyme significantly degrades GABA.ObjectivePresent study is an attempt to characterize the GABAT protein sequences of these bacteria.MethodologySequences of GABAT protein were retrieved from Uniprot database. Sequences were analyzed by Protparam, Gneg-mPLoc, SOSUI, PFP-FunDSeqE, Pepwheel program, PROTEUS and Alphafold and SAVES servers, MEME suite and HDOCK server.ResultsIn healthy individuals gastrointestinal tract (GIT) bacteria, GABAT protein was present in inner-membrane with α helix content (61 and 62%) and β sheet content (5%), 4-helical cytokines functional domains. It has greater number of B-cell epitopes and more complex 3D configuration as compared to MS patients GIT bacterial enzymes.ConclusionPresent study might enable us to modify the GABAT encoding gene and enzyme through site-directed mutagenesis in pathogenic bacteria thus reducing their potential of causing MS.

| S-EPMC10859293 | biostudies-literature

Multiple sclerosis risk variants regulate gene expression in innate and adaptive immune cells.

Project description:At least 200 single-nucleotide polymorphisms (SNPs) are associated with multiple sclerosis (MS) risk. A key function that could mediate SNP-encoded MS risk is their regulatory effects on gene expression. We performed microarrays using RNA extracted from purified immune cell types from 73 untreated MS cases and 97 healthy controls and then performed Cis expression quantitative trait loci mapping studies using additive linear models. We describe MS risk expression quantitative trait loci associations for 129 distinct genes. By extending these models to include an interaction term between genotype and phenotype, we identify MS risk SNPs with opposing effects on gene expression in cases compared with controls, namely, rs2256814 MYT1 in CD4 cells (q = 0.05) and rs12087340 RF00136 in monocyte cells (q = 0.04). The rs703842 SNP was also associated with a differential effect size on the expression of the METTL21B gene in CD8 cells of MS cases relative to controls (q = 0.03). Our study provides a detailed map of MS risk loci that function by regulating gene expression in cell types relevant to MS.

| S-EPMC7283543 | biostudies-literature

Oxygen metabolism and innate immune responses in the gut.

Project description:Epithelial cells of the mucosa provide a first line of defense to prevent the inappropriate translocation of luminal antigens, and therefore contribute significantly to nonspecific innate immunity. In the gastrointestinal (GI) tract, barrier is provided by multiple components of the mucosa, including mucus production, epithelial junctional complexes, and the production of antimicrobial molecules. In recent years, it is better appreciated that tissue oxygen metabolism is key to homeostasis in the mucosa. The intestine, for example, maintains a low baseline Po2 level due to high rates of metabolism, countercurrent blood flow, and the presence of a steep oxygen gradient across the luminal aspect of tissue surface. As a result, hypoxia and hypoxia-inducible factor (HIF)-dependent signaling exists even in the healthy, unperturbed intestinal mucosa. In a number of examples, HIF has been demonstrated both to promote barrier function during homeostasis and to promote resolution of active inflammation. Hypoxia-elicited factors that contribute to innate responses in the mucosa include the transcriptional regulation of mucin genes, junction proteins, and autophagic flux. Here, we review current literature related to hypoxia and innate immunity in health and during mucosal inflammation.

| S-EPMC5792101 | biostudies-other

Innate Immune System and Multiple Sclerosis. Granulocyte Numbers Are Reduced in Patients Affected by Relapsing-Remitting Multiple Sclerosis during the Remission Phase.

Project description:BACKGROUND:Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. The cause of MS is still unknown, and the role of innate immunity is still poorly understood. OBJECTIVE:The goal of this study was to understand whether, compared to healthy controls, the elements of innate immunity are altered in the blood of MS patients in the remitting phase. METHODS:A total of 77 naïve MS patients and 50 healthy controls were included in this cohort study. Peripheral blood samples were collected and analyzed. All the calculations were performed with the statistical system R (r-project.org). RESULTS:The results showed that MS patients had significantly lower relative representations of granulocytes than healthy controls, while the relative representations of monocytes remained unchanged. CD64- and PD-L1-positive granulocytes exhibited a nonsignificant decreasing trend, while granulocytes with other membrane markers remained noticeably unchanged. CONCLUSION:The results of this study suggest that studies of the causes of MS and its treatment should also be focused on the elements of the innate immune response.

| S-EPMC7290702 | biostudies-literature

Oxidative Stress and the Microbiota-Gut-Brain Axis.

Project description:The gut-brain axis is increasingly recognized as an important pathway of communication and of physiological regulation, and gut microbiota seems to play a significant role in this mutual relationship. Oxidative stress is one of the most important pathogenic mechanisms for both neurodegenerative diseases, such as Alzheimer's or Parkinson's, and acute conditions, such as stroke or traumatic brain injury. A peculiar microbiota type might increase brain inflammation and reactive oxygen species levels and might favor abnormal aggregation of proteins. Reversely, brain lesions of various etiologies result in alteration of gut properties and microbiota. These recent hypotheses could open a door for new therapeutic approaches in various neurological diseases.

| S-EPMC6304899 | biostudies-other

Genetics and sex influence peripheral and central innate immune responses and blood-brain barrier integrity.

Project description:Lipopolysaccharide (LPS) is a stimulator of the innate immune system and is routinely used in animal models to study blood-brain barrier (BBB) dysfunction under inflammatory conditions. It is appreciated that both humans and mice have sexually dimorphic immune responses, which could influence the brain's response to a systemic inflammatory insult. Mouse strain is also an important factor that can contribute to pathophysiological responses to inflammatory stimuli. Therefore, we aimed to test whether BBB disruption and the associated cytokine profiles in response to LPS differed in male and female mice from two mouse strains most commonly used in blood-brain barrier studies: CD-1 and C57BL6/J (C57). Mice were treated with saline, a single injection of 0.3, or 3mg/kg LPS, or three injections of 3mg/kg LPS, and studied 28 hours after the first LPS injection. To assay BBB disruption, we utilized the tracer 99mTc-DTPA. A 23-plex panel of cytokines was assayed in brain and blood of the same cohort of mice, which allowed us to compare differences in the levels of individual cytokines as well as correlations among cytokines and 99mTc-DTPA uptake. We found that only the three-injection dose of LPS induced significant BBB disruption in all sexes and strains. The treatment, strain, and sex, as well as treatment-by- strain and treatment-by-sex interactions significantly contributed to the variance. The mean brain/serum ratios of 99mTc-DTPA in the three-injection LPS group were ranked CD-1 male < CD-1 female < C57 male < C57 female. There were significant sex and strain differences in cytokine profiles in brain and blood, and pro-inflammatory cytokines and chemokines in brain were most strongly correlated with 99mTc-DTPA brain/serum ratios.

| S-EPMC6191122 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data