Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nonpeptidergic MrgprD-expressing neurons maintain cutaneous homeostasis via glutamate-mediated mast cell suppression

ABSTRACT: Cutaneous mast cells (MC) mediate numerous skin inflammatory processes and have anatomical and functional associations with sensory afferent neurons. We found that Langerhans cell (LC)-deficient mice have reduced numbers of MrgprD-expressing epidermal nerve endings and manifest enhanced irritant dermatitis due to exaggerated MC degranulation. Ablation of LC or MrgprD-expressing neurons increased expression of a MC gene module including the activating receptor, Mrgprb2, resulting in increased MC degranulation and cutaneous inflammation in multiple models. β-alanine agonism of MrgprD-expressing neurons reduced expression of MC module genes and suppressed MC responses. MrgprD-expressing neurons released glutamate which was increased by MrgprD agonism and decreased in LC-deficient mice. Inhibiting glutamate release or glutamate receptor binding yielded hyperresponsive MC and a genomic state similar to that in mice lacking MrgprD-expressing neurons. These data demonstrate that MrgprD-expressing neurons suppress MC hyperresponsiveness and skin inflammation via glutamate release thereby revealing an unexpected neuro-immune mechanism maintaining cutaneous immune homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE165295 | GEO | 2021/03/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Nonpeptidergic MrgprD-expressing neurons maintain cutaneous homeostasis via glutamate-mediated mast cell suppression

Project description:Nonpeptidergic MrgprD-expressing neurons maintain cutaneous homeostasis via glutamate-mediated mast cell suppression

| PRJNA694030 | ENA

MrgprD-expressing neurons maintain cutaneous mast cell homeostasis

Project description:MrgprD-expressing neurons maintain cutaneous mast cell homeostasis

| PRJNA600963 | ENA

Transcriptional profiling of cutaneous Mrgprd free nerve endings and C-LTMRs

Project description:Cutaneous C-unmyelinated free nerve endings and hair follicles-innervating C-LTMRs convey two opposite aspects of touch sensation: a sensation of pain and a sensation of pleasant touch. The molecular mechanisms underlying these diametrically opposite functions are unknown. Here we used a mouse model that genetically marks C-LTMRs and the free nerve endings MRGPRD+ neurons in combination with fluorescent cell surface labeling, flow cytometry and RNA deep-sequencing technology. Cluster analysis of the RNA-Seq profiles of the purified neuronal subsets revealed 156 and 184 genes differentially expressed in MRGPRD-expressing neurons and C-LTMRs, respectively. 48 MRGPD- and 67 C-LTMRs-enriched genes were validated using a triple staining experiment approach and the Cav3.3 channel, found to be exclusively expressed in C-LTMRs, was validated using electrophysiology. Furthermore, our study greatly expands the molecular characterization of C-LTMRs and suggests that this particular population of neurons shares common transcriptional signatures with A and A low threshold mechanoreceptors. RNA profiles of FACS-sorted subsets of sensory neurons, namely Mrgprd+ neurons (DP, double-positive=IB4+GINIP+), C-LTMRs (IB4-GINIP+) and remaining cells (DN, double-negative=IB4-GINIP-) were generated by deep sequencing in duplicate using Illumina HiSeq 2000.

2015-02-01 | E-GEOD-64091 | biostudies-arrayexpress

Agonism of the glutamate receptor GluK2 suppresses dermal mast cell activation and cutaneous inflammation

Project description:Activation of dermal mast cells through the Mas-related G-protein-coupled receptor B2 receptor (MrgprB2; MrgprX2 in humans) is a key component of numerous inflammatory skin diseases including dermatitis and rosacea. Sensory neurons actively suppress mast cell activation through the regulated release of glutamate resulting in reduced expression of Mrgprb2 and genes associated with proteins found in granules. To determine whether exogenous glutamate receptor agonism could suppress mast cell function, we determined that mast cells have relatively selective expression of the glutamate receptor GluK2. A GluK2-specific agonist, SYM2081, effectively inhibited mast cell degranulation in response to MrgprB2 agonism in vitro in murine mast cells and human skin explants as well as in vivo, following both intradermal and topical administration in mice. Analyses of transcriptomic datasets from SYM2081 treated mast cells using standard differential expression approaches as well as a novel interpretable machine learning technique revealed a previously unrecognized cellular program coordinately regulated by GluK2 agonism. Notably, GluK2 agonism suppressed the expression of Mrgprb2 and genes associated with proliferation. Suppression of mast cell proliferation by SYM2081 exposure was confirmed based on reduced Ki-67 expression and BrdU incorporation in vitro and in vivo. Finally, pretreatment with SYM2081 significantly reduced skin inflammation in murine dermatitis and rosacea models. Thus, agonism of GluK2 represents a promising approach to suppress mast cell activation and may prove beneficial as therapy for inflammatory diseases in which mast cell activation is pathogenic.

2024-12-11 | GSE268986 | GEO

Transcriptional profiling of cutaneous Mrgprd free nerve endings and C-LTMRs

2015-02-01 | GSE64091 | GEO

Agonism of the glutamate receptor GluK2 suppresses dermal mast cell activation and cutaneous inflammation

Project description:Agonism of the glutamate receptor GluK2 suppresses dermal mast cell activation and cutaneous inflammation

| PRJNA1119561 | ENA

GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice

Project description:Agonists and antagonists of the glucose-dependent insulinotropic polypeptide receptor (GIPR) enhance body weight loss induced by glucagon-like peptide-1 receptor (GLP-1R) agonism. However, while GIPR agonism decreases body weight and food intake in a GLP-1R-independent manner via GABAergic GIPR+ neurons, it remains unclear whether GIPR antagonism affects energy metabolism via a similar mechanism. Here we show that the body weight and food intake effects of GIPR antagonism are eliminated in mice with global loss of either Gipr or Glp-1r but are preserved in mice with loss of Gipr in either GABAergic neurons of the central nervous system or peripherin-expressing neurons of the peripheral nervous system. Single-nucleus RNA-sequencing shows opposing effects of GIPR agonism and antagonism in the dorsal vagal complex, with antagonism, but not agonism, closely resembling GLP-1R signalling. Additionally, GIPR antagonism and GLP-1R agonism both regulate genes implicated in synaptic plasticity. Collectively, we show that GIPR agonism and antagonism decrease body weight via different mechanisms, with GIPR antagonism, unlike agonism, depending on functional GLP-1R signalling.

2025-03-12 | GSE288514 | GEO

Generation of Locus Coeruleus Norepinephrine Neurons from Human Pluripotent Stem Cells [snRNA-seq]

Project description:Central norepinephrine (NE) neurons, mainly located in the Locus coeruleus (LC), play roles in a wide range of behavioral and physiological processes. How the human LC-NE neurons develop and what roles they play in the pathophysiology of human diseases is poorly understood, partly due to the unavailability of functional human LC-NE neurons. Here we established a technology for efficient generation of LC-NE neurons from human pluripotent stem cells by identifying a novel role of ACTIVIN A in regulating the LC-NE transcription factors in the dorsal rhombomere 1 (r1) progenitors. The in vitro generated human LC-NE neurons not only display extensive axonal arborization and release/uptake NE, but also exhibit the pacemaker activity, calcium oscillation, and in particular chemoreceptor activity in response to CO2. Multiple timepoint single nucleus RNA-Seq (snRNA-Seq) analysis captured the dynamic NE differentiation process, confirmed the NE cell population and revealed the differentiation trajectory from hindbrain progenitors to NE neurons via ASCL1 expressing precursor stage. The LC-NE neurons engineered with a NE sensor reliably reported the extracellular NE level. The availability of functional human LC-NE neurons enables investigation of their roles in the pathogenesis of and development of therapeutics for neural psychiatric and degenerative diseases.

2023-08-24 | GSE221988 | GEO

Distinct nociceptor roles in inflammation and itch revealed by subset-specific transcriptomic adaptation

Project description:This study identifies two distinct subsets of sensory neurons that separately regulate itch and inflammation in allergic contact dermatitis. MrgprD⁺ nonpeptidergic neurons adopt a transient regenerative program during inflammation and are essential for itch behavior, while Trpv1⁺ peptidergic neurons limit inflammation by restraining neutrophil infiltration. These findings uncover parallel, nonredundant neuronal circuits that independently control inflammatory and pruritic responses in the skin.

2026-04-15 | GSE315295 | GEO

N-acetyl-D-glucosamine is an oncometabolite modulating mast cell effector functions by chromatin remodeling

Project description:We investigated the metabolic regulation of mast cell (MC) functions to control them. MCs are sentinels of the immune system with functions involved not only in host defense but also, if not properly controlled, in MC disorders such as systemic mastocytosis (SM). We identified N-acetyl-D-glucosamine (GlcNAc or NAG) as both a circulating biomarker for SM severity and an oncometabolite that promotes uncontrolled degranulation and proliferation of MCs expressing the Kit kinase domain mutant allele, D816V, that is both an oncogene and characterizes patients with SM. Given the known role of GlcNAc-related protein glycosylation in modifying factors involved in epigenetic regulation of gene expression and the effects of GlcNAc on neoplastic MCs effector functions, we asked whether the increased susceptibility of KIT D816V MCs to GlcNAc was due to chromatin state changes.

2023-04-20 | GSE149106 | GEO

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