Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intestinal inflammation promotes gut commensal-specific CD4 T cell to initiate molecular mimicry-mediated neuroinflammation

ABSTRACT: The microbiota has been recognized as a critical contributor to various diseases, with multiple reports of changes in the composition of the gut microbiome in the context of not only inflammatory bowel disease (IBD), but also neurodegenerative diseases. These microbial shifts can exert systemic effects by altering the release of specific metabolites into the bloodstream, and the gastrointestinal microbiota has further been reported to exhibit immunomodulatory activity through the activation of innate and adaptive immunity. However, it remains unclear how the intestinal microbiota contributes to inflammation in the central nervous system (CNS), where these microorganisms are typically absent. Here, we report that ileum- and cecum-colonizing segmented filamentous bacteria (SFB)-specific T cells can induce inflammation in both the intestines and the CNS. Commensal-specific CD4 T cells that are dysregulated in the inflamed gut can become licensed to infiltrate into the CNS irrespective of their antigen specificity and have the potential to be re-stimulated by host protein-derived antigens in the CNS via molecular mimicry, whereupon they produce high levels of GM-CSF, TNFa, IFNg, and IL-17A, triggering neurological damage. We find that these infiltrated commensal-specific CD4 T cells initiate CNS inflammation by activating microglia through their IL-23R dependent encephalitogenic program and their IL-23R-independent GM-CSF production. Together, our findings reveal a potential mechanism whereby perturbation of commensal-specific T cells can contribute to extraintestinal inflammation.

ORGANISM(S): Mus musculus

PROVIDER: GSE295689 | GEO | 2025/05/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Intestinal inflammation promotes gut commensal-specific CD4 T cell to initiate molecular mimicry-mediated neuroinflammation

Project description:The microbiota has been recognized as a critical contributor to various diseases, with multiple reports of changes in the composition of the gut microbiome in the context of not only inflammatory bowel disease (IBD), but also neurodegenerative diseases. These microbial shifts can exert systemic effects by altering the release of specific metabolites into the bloodstream, and the gastrointestinal microbiota has further been reported to exhibit immunomodulatory activity through the activation of innate and adaptive immunity. However, it remains unclear how the intestinal microbiota contributes to inflammation in the central nervous system (CNS), where these microorganisms are typically absent. Here, we report that ileum- and cecum-colonizing segmented filamentous bacteria (SFB)-specific T cells can induce inflammation in both the intestines and the CNS. Commensal-specific CD4 T cells that are dysregulated in the inflamed gut can become licensed to infiltrate into the CNS irrespective of their antigen specificity and have the potential to be re-stimulated by host protein-derived antigens in the CNS via molecular mimicry, whereupon they produce high levels of GM-CSF, TNFa, IFNg, and IL-17A, triggering neurological damage. We find that these infiltrated commensal-specific CD4 T cells initiate CNS inflammation by activating microglia through their IL-23R dependent encephalitogenic program and their IL-23R-independent GM-CSF production. Together, our findings reveal a potential mechanism whereby perturbation of commensal-specific T cells can contribute to extraintestinal inflammation.

2025-05-07 | GSE295643 | GEO

Effect of metronidazole on microglial gene expression and gut microbiome composition in the 5XFAD mice model of Alzheimer's disease

Project description:The gut microbiota and innate immune system play critical roles in Alzheimer’s disease (AD). Bacteroides is elevated in AD patients and correlates with cerebrospinal fluid levels of Aβ and tau. We found that increased amyloid-β (Aβ) plaques in Bacteroides fragilis treated APP/PS1-21 mice were associated with altered cortical expression Aβ processing genes. B. fragilis suppressed peripheral CD4+ T cell production of GM-CSF and IL-4 and transcriptional changes in microglia related to GM-CSF and IL-4 signaling, phagocytosis, and protein degradation. Furthermore, B. fragilis impaired the microglial uptake of intracranially injected Aβ42, whereas Erysipelotrichaceae strains increased uptake. Depleting murine Bacteroidetes with metronidazole decreased amyloid load in aged 5xFAD mice, increased CD4+ T cell GM-CSF production, and activated microglial pathways related to cytokine signaling, phagocytosis and lysosomal degradation. These data suggest that the gut microbiome may contribute to AD pathogenesis by suppressing peripheral cytokines and microglia phagocytic function, leading to impaired immune-mediated Aβ clearance.

2024-10-12 | GSE215439 | GEO

Effect of Bacteroides fragilis administration on microglia in WT and the APP-PS1 model of Alzheimer's disease [Bfrag]

2024-10-12 | GSE215438 | GEO

Single-cell clonotype tracing identifies a stem-like intestinal Th17 population that gives rise to pathogenic effector T cells during autoimmunity

Project description:While intestinal Th17 cells are critical for maintaining tissue homeostasis, recent studies in both humans and mice have implicated their roles in the development of extra-intestinal autoimmune diseases such as multiple sclerosis. However, the mechanisms by which tissue Th17 cells mediate these dichotomous functions remain unknown. Here, we characterized the heterogeneity, plasticity, and migratory phenotypes of tissue Th17 cells in vivo by combining fate mapping with single-cell RNA sequencing to profile the transcriptomes and TCR clonotypes of over 84,000 Th17 cells at homeostasis and during CNS autoimmune inflammation. Inter- and intra-organ single-cell analyses revealed a homeostatic, stem-like TCF1+ IL-17+ SLAMF6+ population that traffics to the intestine where it is maintained by the microbiota, providing a ready-reservoir for the IL-23-driven generation of encephalitogenic GM-CSF+ IFNγ+ CXCR6+ T cells. Our study defines a direct relationship in vivo between IL-17+ non-pathogenic and GM-CSF+ and IFNγ+ pathogenic Th17 populations and provides, for the first time, a mechanism by which homeostatic intestinal Th17 cells direct extra-intestinal autoimmune disease.

2021-11-05 | GSE188320 | GEO

Expression data from in vitro differentiated MDSC

Project description:MDSC (myeloid-derived suppressor cells) can be differentiated in vitro using IL-6 and GM-CSF. To identify the specific role of IL-6 in this process, we used microarray to compare MDSC differentiated with IL-6 and GM-CSF to MDSC differentiated with GM-CSF alone. We have found genes and pathways that are up- or downregulated when IL-6 is present.

2020-08-19 | GSE148293 | GEO

E-MTAB-8550

Project description:Gut microbiota and gallstone formation - cohousing study

2020-01-10 | E-MTAB-8550 | ExpressionAtlas

Expression data from oxaliplatin-treated tumors from mice pre-treated or not with antibiotics cocktail

Project description:The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression and treatment of cancer, but it remains unclear whether commensal bacteria affect inflammation in the sterile tumor microenvironment. Here we show that disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy. In antibiotic-treated or germ-free mice, tumor-infiltrating myeloid-derived cells responded poorly to therapy, resulting in lower cytokine production and tumor necrosis after CpG-oligonucleotide treatment, and deficient production of reactive oxygen species and cytotoxicity following chemotherapy. Thus, optimal responses to cancer therapy require an intact commensal microbiota that mediates its effects by modulating myeloid-derived cell functions in the tumor microenvironment. These findings underscore the importance of the microbiota in the outcome of disease treatment. Oxaliplatin treatment induces expression of pro-inflammatory genes, which are inhibited by antibiotic pretreatment. Our goal was to ascertain the effect of antibiotic on the tumor gene expression profile prior to treatment and early on after the treatment with chemotherapy (oxaliplatin). The time points were selected t

2013-12-03 | E-GEOD-51414 | biostudies-arrayexpress

E-GEOD-60528

Project description:Mouse GM-CSF-related alveolar macrophage genome-wide expression data

2015-07-29 | E-GEOD-60528 | ExpressionAtlas

NK cell-derived GM-CSF is critical for enhancing pathological arthritis

Project description:GM-CSF is involved in immune complex (IC)-mediated arthritis. However, little is known about what is the cellular source of GM-CSF and how it is regulated during IC-mediated inflammation. Using novel GM-CSF reporter mice, we show that NK cells produce GM-CSF during an IC-mediated model of inflammatory arthritis. NK cells promoted STIA in a GM-CSF-dependent manner, as deletion of NK cells and selective removal of GM-CSF production by NK cells abrogated disease. Furthermore, we show that myeloid cell activation by GM-CSF is restrained by induction of JAK/STAT checkpoint inhibitor cytokine-inducible SH2-containing protein, CIS. Myeloid cells from CIS-deficient mice had exaggerated responses to GM-CSF, and these mice develop exacerbated STIA. Our data suggest that tissue NK cells may amplify joint inflammation in arthritis via GM-CSF production and thus represent a novel target in IC-mediated pathology. Endogenous CIS provides a key brake on signaling through the GM-CSF receptor and strategies that boost its function may provide an alternative anti-inflammatory approach.

2020-02-19 | PXD012794 | Pride

microbiota regualtion of miRNA

Project description:This experiment was investigating how gut commensal bacteria and intestinal inflammation affect miRNA expression. We analyzed miRNA expression of spleen and intestine from specific pathogen free (SPF) B6 mice, germ-free (GF) B6 mice, and IL-10 knockout mice which have severe colitis by microarray. Thus we have total 6 samples: GF spleen; GF intestines; SPF spleen; SPF intestine; IL-10 KO spleen and IL-10 KO intestine. We directly isolated RNA from whole spleens or intestines without any treatments, and then did microarray analysis.

2011-11-23 | E-MEXP-3406 | biostudies-arrayexpress

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