Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Folate Receptor Beta Regulates Macrophage NLRP3 Inflammasome Activation and Pyroptosis in a Folate-Independent Manner [methylation array]

ABSTRACT: Folate receptor beta (FRb), encoded by FOLR2, is selectively expressed in monocytes and macrophages, yet its function in innate immune signaling remains poorly defined. Here, we identify FRb as a novel regulator of NLRP3 inflammasome activation and pyroptosis in human THP-1 macrophages. Using CRISPR/Cas9-mediated gene deletion, we show that loss of FOLR2 impairs caspase-1 activation, gasdermin D cleavage, and IL-1b release in response to multiple NLRP3 stimuli, without altering pro-IL-1 b induction. These defects were not rescued by exogenous folate and were independent of extracellular folate concentrations. Mechanistically, FOLR2 deletion reduced potassium efflux and downregulated multiple potassium channel genes. Single-cell RNA sequencing revealed broad transcriptional repression in FRb-deficient macrophages, including genes involved in inflammasome signaling and ion transport. Genome-wide methylation profiling showed increased CpG hypermethylation in FOLR2-deficient cells, consistent with reduced transcriptional activity. Our findings indicate that FRb promotes NLRP3 activation in a folate-independent manner by regulating transcription and K⁺ efflux in macrophages. These data reveal a previously unrecognized immunoregulatory role for FRb with implications for host defense, autoimmunity, and macrophage function in tissue microenvironments such as the tumor or placenta.

ORGANISM(S): Homo sapiens

PROVIDER: GSE301573 | GEO | 2026/04/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Folate Receptor Beta Regulates Macrophage NLRP3 Inflammasome Activation and Pyroptosis in a Folate-Independent Manner

Project description:Folate receptor beta (FRb), encoded by FOLR2, is selectively expressed in monocytes and macrophages, yet its function in innate immune signaling remains poorly defined. Here, we identify FRb as a novel regulator of NLRP3 inflammasome activation and pyroptosis in human THP-1 macrophages. Using CRISPR/Cas9-mediated gene deletion, we show that loss of FOLR2 impairs caspase-1 activation, gasdermin D cleavage, and IL-1b release in response to multiple NLRP3 stimuli, without altering pro-IL-1 b induction. These defects were not rescued by exogenous folate and were independent of extracellular folate concentrations. Mechanistically, FOLR2 deletion reduced potassium efflux and downregulated multiple potassium channel genes. Single-cell RNA sequencing revealed broad transcriptional repression in FRb-deficient macrophages, including genes involved in inflammasome signaling and ion transport. Genome-wide methylation profiling showed increased CpG hypermethylation in FOLR2-deficient cells, consistent with reduced transcriptional activity. Our findings indicate that FRb promotes NLRP3 activation in a folate-independent manner by regulating transcription and K⁺ efflux in macrophages. These data reveal a previously unrecognized immunoregulatory role for FRb with implications for host defense, autoimmunity, and macrophage function in tissue microenvironments such as the tumor or placenta.

2026-04-15 | GSE301541 | GEO

FADD is a new protein secreted unconventionally following classical NLRP3 inflammasome activation

Project description:NLRP3 inflammasome assembles in response to stress or danger signals and leads to unconventional secretion of proinflammatory IL-1. FADD is an NLRP3 inflammasome component. Here we found that classical NLRP3 inflammasome activation in human monocytes/macrophages induced FADD secretion, which required potassium efflux, functional NLRP3 sensor, ASC adaptor and caspase-1 scaffold molecule. FADD is a leaderless protein unconventionally secreted through plasma membrane-derived microvesicles. Blood-derived monocytes from rheumatoid arthritis (RA) patients secreted more FADD following NLRP3 inflammasome activation than those from healthy donors, and we found increased levels of FADD in the sera (ESPOIR cohort) and synovial fluids from RA patients. Levels of synovial FADD correlated with the inflammatory status of the joint. These data reveal that FADD secretion occurs during inflammatory disease in vivo.

2019-02-28 | PXD008168 | Pride

OXSR1 inhibits inflammasome activation by limiting potassium efflux during mycobacterial infection

Project description:Pathogenic mycobacteria inhibit inflammasome activation as part of their pathogenesis. While it is known that potassium efflux is a trigger for inflammasome activation, the interaction between mycobacterial infection, potassium efflux and inflammasome activation has not been investigated. Here we use Mycobacterium marinum infection of zebrafish embryos to demonstrate that pathogenic mycobacteria upregulate the host WNK signalling pathway kinases SPAK and OXSR1 which control intracellular potassium balance. We show that genetic depletion or inhibition of OXSR1 decreases bacterial burden and intracellular potassium levels. The protective effects of OXSR1 depletion are mediated by NLRP3 inflammasome activation and are dependent on caspase-mediated release of IL-1β and the downstream activation of protective TNF-α. The elucidation of this druggable pathway to potentiate inflammasome activation provides a new avenue for the development of host-directed therapies against intracellular infections.

2022-05-05 | PXD030631 | Pride

Genome-wide CRISPR/Cas9 knockout screen for novel regulators of mechanical stress on NLRP3 inflammasome activation

Project description:Immune cells sense the microenvironment to fine-tune their inflammatory responses. Patients with cryopyrin associated periodic syndrome (CAPS), caused by mutations in the NLRP3 gene, present auto-inflammation and its manifestation is largely dependent on environmental cues. However, the underlying mechanisms are poorly understood. Here, we uncover that KCNN4, a calcium-activated potassium channel, links PIEZO-mediated mechanotransduction to NLRP3 inflammasome activation. Yoda1, a PIEZO1 agonist, lowers the threshold for NLRP3 inflammasome activation. PIEZO-mediated sensing of stiffness and shear stress increases NLRP3-dependent inflammation. Myeloid-specific deletion of PIEZO1/2 protects mice from gouty arthritis. Activation of PIEZO1 triggers calcium influx, which activates KCNN4 to evoke potassium efflux promoting NLRP3 inflammasome activation. Activation of PIEZO signaling is sufficient to activate the inflammasome in cells expressing CAPS-causing NLRP3 mutants via KCNN4. Finally, pharmacologic inhibition of KCNN4 alleviates auto-inflammation in CAPS patient cells and in CAPS-mimicking mice. Thus, PIEZO-dependent mechanical inputs augment inflammation in NLRP3-dependent diseases including CAPS.

2023-10-26 | GSE246208 | GEO

Cytosolic sodium accumulation is a common danger signal triggering NLRP3 inflammasome activation

Project description:Detecting noxious molecules within the endo/lysosomal system is essential for maintaining cellular integrity. Here, we identify acute cytosolic sodium accumulation as a key trigger for NLRP3 inflammasome activation. Large clostridial toxins, as well as monosodium urate and silica crystals, rapidly elevate cytosolic sodium by promoting its release from the endo/lysosomal system, triggering concurrent potassium efflux and extracellular sodium influx. This rise in cytosolic sodium disrupts endocytic trafficking by collapsing the sodium gradient across endosomal membranes, leading to peripheral redistribution and activation of NLRP3. Importantly, non-particulate stimuli, including nigericin, also activate NLRP3 by this sodium-dependent mechanism. These findings position cytosolic sodium as a key downstream effector of potassium efflux and a central signal for NLRP3 activation across diverse stimuli.

2026-05-21 | GSE297761 | GEO

Folate Receptor Beta Regulates Macrophage NLRP3 Inflammasome Activation and Pyroptosis in a Folate-Independent Manner

Project description:Folate Receptor Beta Regulates Macrophage NLRP3 Inflammasome Activation and Pyroptosis in a Folate-Independent Manner

| PRJNA1285405 | ENA

Mitochondrial dysfunction caused by bacterial outer membranes vesicles activates intrinsic apoptosis and inflammation

Project description:Sensing of microbes activates the immune system, depending on functional mitochondria. However, pathogenic bacteria inhibit mitochondria activity by delivering toxins via outer membrane vesicles (OMVs). How innate immune cells respond to pathogenic microbes that target mitochondria remains unclear. Here, we show that macrophages induce mitochondrial apoptosis and the NLRP3 inflammasome in response OMVs. Macrophages treated with OMVs and toxins that cause mitochondria dysfunction cease host protein translation which depletes pro-survival BCL-2 family member, MCL-1, and induces BAK-dependent mitochondrial apoptosis. Mitochondrial apoptosis and potassium ion efflux activate the NLRP3 inflammasome after OMV exposure. Importantly, mitochondrial apoptosis modulates IL-1 serum levels in response to OMVs. Our data highlight how innate immune cells sense infections by monitoring mitochondrial health.

2020-07-30 | PXD018563 | Pride

Butyrate and propionate are microbial danger signals that activate the NLRP3-inflammasome in human macrophages in the presence of TLR stimulation

Project description:Short chain fatty acids (SCFAs) are immunomodulatory compounds produced by the microbiome through fermentation of dietary fibre. Although they are generally considered beneficial for gut health, patients suffering from inflammatory bowel disease (IBD) have shown poor tolerance to fibre-rich diets, suggesting that SCFAs may have contrary effects under inflammatory conditions. To investigate this, we examined the effect of SCFAs on human macrophages in the presence of toll-like receptor agonists. In contrast to their anti-inflammatory effects under steady state conditions, we observed that the SCFAs butyrate and propionate triggered the activation of the NLRP3 inflammasome when added in conjunction with TLR agonists. Mechanistically, butyrate and propionate activated NLRP3 by inhibiting HDACs 1-3 and 10, leading to an uneven distribution of histone hyperacetylation that resulted in alterations in the transcriptome. Specifically, there was a lack of hyperacetylation at the loci of the CFLAR and IL10 genes, two important inhibitors of NLRP3 inflammasome activation. The concurrent loss of transcription and protein expression of cFLIP and IL-10 enabled caspase-8-dependent NLRP3-inflammasome activation. SCFA-driven NLRP3 activation did not require potassium efflux and did not result in cell death but rather triggered hyperactivation and IL-1b release. Our findings demonstrate that butyrate and propionate are bacterially-derived, viability-dependent danger signals (vita-PAMPs) that regulate NLRP3 inflammasome activation through epigenetic modulation of the inflammatory response.

2024-08-19 | GSE248578 | GEO

Butyrate and propionate are microbial danger signals that activate the NLRP3-inflammasome in human macrophages in the presence of TLR stimulation

2024-08-19 | GSE248577 | GEO

Folate Receptor Beta Regulates Macrophage NLRP3 Inflammasome Activation and Pyroptosis in a Folate-Independent Manner [methylation array]

Project description:Folate Receptor Beta Regulates Macrophage NLRP3 Inflammasome Activation and Pyroptosis in a Folate-Independent Manner [methylation array]

| PRJNA1285497 | ENA

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