Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

KMT2D maintains Treg homeostasis and protects against inflammatory diseases by regulating the purinergic channel P2X7 level

ABSTRACT: Regulatory T (Treg) cells are essential for maintaining immune homeostasis and tolerance through the prevention of inflammatory and autoimmune responses. The histone methyltransferase KMT2D is indispensable for induced Treg (iTreg) cell differentiation, its role in the differentiation and function of Treg cells in vivo has remained largely unknown. Here, we demonstrate that KMT2D is critical for the differentiation and function of effector activated Treg (aTreg) cells. We found that KMT2D deficiency in Treg cells impairs aTreg generation and exacerbates inflammatory conditions, such as allergic airway inflammation and colitis. Mechanistically, KMT2D regulates aTreg differentiation through TCR signaling. Furthermore, KMT2D modulates Ca2+ influx by promoting the expression of purinergic receptor P2X7 through H3K4me3 deposition. Collectively, our fundings highlight a pivotal role for KMT2D in Treg cell homeostasis and function, potentially offering a new therapeutic strategy for treating inflammatory diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE316049 | GEO | 2026/01/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE316049_RAW.tar	Raw
	filelist.txt	Txt

Items per page:

1 - 3 of 3

Similar Datasets

The ATP-P2X7 signaling axis is dispensable for obesity-associated inflammasome activation in adipose tissue

Project description:Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7), may play a role in inflammasome activation in adipose tissue in obesity. Our data show that inflammasome is activated in adipose tissue upon 8-week feeding of 60% HFD, coinciding with the onset of hyperglycemia and hyperinsulinemia as well as the induction of P2X7 in adipose tissue. Unexpectedly, P2X7-deficient animals on HFD exhibit no changes in metabolic phenotypes, nor in inflammatory responses or inflammasome activation when compared to the wildtype controls. Similar observations have been obtained in hematopoietic cell-specific P2X7-deficient animals generated by bone marrow transplantation. Thus, we conclude that inflammasome activation in adipose tissue in obesity coincides with the onset of hyperglycemia and hyperinsulinemia, but unexpectedly, is not mediated by the ATP-P2X7 signaling axis. The nature of the inflammasome-activating danger signal(s) in adipose tissue in obesity remains to be characterized. Wild type and P2X7 knockout mice were fed a low fat diet (chow) or high fat diet for 12 weeks. After the diet intervention period, the animals were killed and epididymal white adipose tissue was removed. Total RNA was isolated and subjected to gene expression profiling.

2012-02-24 | E-GEOD-36033 | biostudies-arrayexpress

The ATP-P2X7 signaling axis is dispensable for obesity-associated inflammasome activation in adipose tissue

2012-02-24 | GSE36033 | GEO

Nanobody-based in vivo blockade of the P2X7 ion channel uncovers a hitherto unknown large subpopulation of parenchymal kidney TRM and NKT cells

Project description:The P2X7 ion channel, a key sensor of sterile inflammation, has been implicated as a therapeutic target in glomerulonephritis and P2X7-antagonistic nanobodies can attenuate experimental glomerulonephritis. However, little is known about the expression of P2X7 on renal immune cells. We used i.p. injection of nanobodies in mice followed by flow cytometry analysis of parenchymal T cells and RNA-sequencing to elucidate the expression and function of P2X7 on parenchymal and vascular immune cells in the mouse kidney. We show that parenchymal T cells, including a large subset NKT cells and tissue-resident memory T cells, display much higher cell surface levels of P2X7 than vascular T cells. These parenchymal T cells are highly sensitive to NAD+-induced cell death unless injection of P2X7-antagonistic nanobodies was performed before cell preparation. Remarkably, within 30 min after a single intraperitoneal injection of P2X7-blocking nanobodies, P2X7 is fully occupied by the injected nanobodies on parenchymal T cells in the kidney. This results in an effective protection of these cells from NAD+-induced cell death. Conversely, systemic injection of NAD+ that mimics sterile inflammation results in the selective depletion of P2X7hiCD69hi T cells from the kidney parenchyma. In summary, our study uncovers a novel purinergic regulatory mechanism affecting kidney resident T cell populations.

2024-12-04 | GSE241191 | GEO

Retrieval of inflammation-compromised periodontal ligament stem cells from dysfunction by exosomes derived from P2X7 receptor gene-modified cells

Project description:Exosomes derived from P2X7 gene modified stem cells could enhance the osteogenic differentiation of periodontal ligament stem cells under inflammatory cultural conditions. In order to identify differentially expressed miRNAs between Exs-Ad-P2X7 and Exs-Ad- control, total RNA from exosomes were extracted by TRIzol™ Reagent (Invitrogen) according to the instructions. Then, miRNA profile of Exs-Ad-P2X7 and Exs-Ad-control form 3 different individuals were sequenced by Agilent miRNA Microarray System and further confirmed by real-time PCR.

2020-10-28 | GSE140356 | GEO

Gene expression profile of Wild Type (WT) and P2x7 knockout (P2X7-KO) leukemia leukemia-initiating cells Transcriptomes

Project description:To determine the underlying molecular mechanisms that control the homing and self-renewal activities of P2x7-null Mac-1+c-Kit+ LICs, WT and P2x7-null LICs were WT and P2x7-KO were sorted by flow cytometry, followed by the extraction of total RNA and subjected to the RNA-sequencing.

2023-11-30 | GSE162468 | GEO

BACH2 is repurposed following Treg lineage commitment to drive the functional quiescence and maintenance of resting Treg cells

Project description:In various tissues, cellular homeostasis is achieved by functionally quiescent stem cells which self renew while giving rise to differentiated progeny. Regulatory T (Treg) cells are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification but its function following lineage commitment is unresolved. Here, we show Bach2 is highly expressed in lineage-committed rTreg cells but is downregulated in aTreg cells, and upon inflammation. BACH2 binds to AP-1 sites within Treg genomes and its high expression within rTreg cells functions to restrain their TCR-driven activation and differentiation into aTreg cells. As a consequence, cell-autonomous BACH2 expression is required following Treg lineage commitment for the functional quiescence and long-term maintenance of Treg cell populations and for immune homeostasis. This SuperSeries is composed of the SubSeries listed below.

2020-05-12 | GSE128176 | GEO

Distribution of genome-wide BACH2 or JunD binding sites identified by ChIP-Seq in iTreg cells

Project description:In various tissues, cellular homeostasis is achieved by functionally quiescent stem cells which selfrenew while giving rise to differentiated progeny. Regulatory T (Treg) cells are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification but its function following lineage commitment is unresolved. Here, we show Bach2 is highly expressed in lineage-committed rTreg cells but is downregulated in aTreg cells, and upon inflammation. BACH2 binds to AP-1 sites within Treg genomes and its high expression within rTreg cells functions to restrain their TCR-driven activation and differentiation into aTreg cells. As a consequence, cell-autonomous BACH2 expression is required following Treg lineagecommitment for the functional quiescence and long-term maintenance of Treg cell populations and for immune homeostasis.

2020-05-12 | GSE127695 | GEO

P2X7 receptor-dependent microRNA expression profile in the brain following status epilepticus in mice

Project description:We explored the microRNA expression profile in mice lacking the P2X7 receptor before and after seizures. Genome-wide microRNA profiling was performed using hippocampi from wild-type and P2X7 knock-out mice following status epilepticus induced by intraamygdala kainic acid. This revealed that genetic deletion of the P2X7 receptor results in distinct patterns of microRNA expression. Specifically, we found that in vehicle-injected control mice the lack of P2X7 resulted in the up-regulation of 50 microRNAs and down-regulation of 35 microRNAs. Post-status epilepticus, P2X7 deficiency let to the up-regulation of 44 microRNAs while 13 microRNAs were down-regulated. Moreover, there was only limited overlap between identified P2X7-dependent microRNAs between control conditions and post-status epilepticus, suggesting P2X7 regulating the expression of different microRNAs during normal physiology and pathology. Bioinformatics analysis found that genes targeted via P2X7-dependent microRNAs were particularly overrepresented within pathways involved in intracellular signalling, inflammation and cell death, processes repeatedly linked to P2X7. Moreover, whereas genes involved in signalling pathways and inflammation were common among up-and down-regulated P2X7-dependent miRNAs during physiological and pathological conditions, genes associated with cell death seemed to be restricted to up-regulated miRNAs during both physiological conditions and post-status epilepticus. Taken together, our results demonstrate that P2X7 impacts on the expression profile of microRNAs in the brain, thereby possibly contributing to both the maintenance of normal cellular homeostasis and pathological processes.

2020-06-25 | GSE153204 | GEO

Genetic deletion of P2X7 receptors causes genome-wide alteration of gene expression and results in antidepressant phenotype in mice amygdale

Project description:The purpose of the study was to explore the role of P2X7 receptors (P2X7R) in mood related behavior we have employed whole genome microarray expression profiling as a discovery platform.To identify genes affected by the genetic deletion of P2X7 receptors in the mouse amygdala we performed gene expression microarray analysis. For validation of differentially expressed genes, we performed TaqMan real-time RT-PCR.Our microarray studies have identified 7217 transcripts that were significantly affected by the deficiency of P2X7 receptor. Validation experiments revealed that among these genes at least 30 genes could be associated to synaptic signaling, neuroplasticity and thereby to the pathogenesis of depression (e.g. beta and gamma subunits of GABAA receptor, ionotropic glutamate receptors, M-NM-12 adrenergic receptor, which were down regulated in KO mice). 287 transcripts were found be more than two-fold over-expressed in the LPS treated groups which can be classified according to their inflammatory biological function: Il4ra, Saa1, chemokine ligands. Intraperitoneal injection of LPS induced alteration of gene expression in mouse amygdala was measured at 6 hours after exposure to doses of 250M-BM-5g/kg. Four independent experiments were performed for each of the four experimental groups (wild type mice and P2X7R -/- KO and saline treatment and LPS treatment).

2011-03-31 | E-GEOD-21218 | biostudies-arrayexpress

EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling.

Project description:The phagocyte NADPH oxidase is critical for host defence, and EROS (Essential for Reactive Oxygen Species) protein is indispensable for expression of its gp91phox-p22phox heterodimer. EROS deficiency in humans is a recently described cause of chronic granulomatous disease (CGD), but its mechanism of action remains unknown. We show EROS binds the immature 58kDa gp91phox directly prior to glycosylation and heme incorporation, thus preventing its degradation. EROS interacts with the oligosaccharyl transferase complex (OST) present at the endoplasmic reticulum. Inhibition of the OST complex suppresses EROS-mediated stabilisation of the 58kDa, providing insight into the early steps of gp91phox biosynthesis. EROS also regulates the purine receptors P2X7 and P2X1 through direct interactions. Accordingly, lack of EROS results in markedly abnormal P2X7 signalling, inflammasome activation and T cell responses. The loss of both the phagocyte respiratory burst and P2X7 signalling lead to resistance to influenza infection. Our work identifies EROS as the first described highly selective chaperone controlling key proteins in innate and adaptive immunity. It has profound implications for immune physiology, immunodeficiency and gene therapy.

2022-11-30 | PXD025149 | Pride

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