Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease [Bulk RNA-seq]

ABSTRACT: Inflammatory skin diseases are spurred by unchecked immune-epithelial circuits. Although the function of cytokine and chemokine signals in facilitating this crosstalk is well established, the specific metabolic mediators involved and their simultaneous contribution to dysregulation of these two distinct cellular compartments is unclear. Here, we employed scRNA-seq, spatial transcriptomics, and immunofluorescence across multiple disease indications to elucidate a dysfunctional epithelial state marked by Hypoxia Inducible Factor 1 alpha (HIF1⍺). Ex vivo HIF1⍺ blockade of human Psoriasis (PsO) lesions led to a reduction in pathological gene expression via modulation of glucose metabolism. Epidermal-specific loss of HIF1⍺ or its transcriptional target, glucose transporter 1, curtailed both epidermal pathology and the cutaneous immune response in murine PsO. Glycolytic metabolism sustained epithelial hyperproliferation and differentiation, while lactate, its terminal product, was crucial for sustaining Type 17 response. Notably, inhibition of lactate dehydrogenase A or the lactate transporters MCT1/4 selectively attenuated the Type 17 response, underscoring a divergent requirement for glucose and lactate in epithelial and immune cells, respectively. Collectively, these findings identify therapeutically targetable immune-epithelial circuits by unveiling a remarkable coordination of metabolic processed between the epithelial and immune compartments in inflammatory skin disease.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE237767 | GEO | 2024/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptome analysis of atopic dermatitis and psoriasis lesional skin

Project description:Purpose: To deeply understand the clinical as well as pathogenetic differences, we have analyzed the genes involved in the epidermal lipid synthesis, epidermal development process and immune responses in the skin of AD and PSO patients. Materials and Methods: We have compared the transcriptomes of lesional skin (epidermis+dermis) from 2 adults AD patients and 2 PSO patients by high-throughput complementary DNA sequencing (RNA-seq). For the gene expression estimation, Cufflinks v2.1.1 was used that is the gene annotation database of Ensembl release 72.

2021-06-08 | GSE176279 | GEO

Transcriptome of MTB H37Rv in glucose L-lactate and pyruvate

Project description:Mycobacterium tuberculosis has specialised its metabolism to reside extra- and intra-cellularly in the human host. Nutrient availability and their concentrations can vary dramatically in these niches. Lactate is abundant during infection and it is an important signalling molecule regulating the immune response. In addition, lactate is abundant in blood, epithelial mucosa and a number of other relevant compartments in the host. Interestingly, previous studies have demonstrated that lactate and one of its possible first degradation products, pyruvate, allow superior growth compared to glucose and fatty acids in vitro for M. tuberculosis. Based on this information, we performed a "multi-omics" investigation to study the metabolism of pyruvate and lactate in M. tuberculosis. We employed TraDIS, transcriptomics, proteomics and stable isotopic labelling coupled with mass spectrometry-based metabolomics. Our studies reveal the structure of M. tuberculosis metabolic network associated with catabolism of pyruvate and lactate. Together these findings lead us to reconsider some well-accepted "truths" on carbon metabolism in M. tuberculosis.

2019-11-25 | GSE116859 | GEO

HIF1/2-exerted control over glycolysis but not OxPHOS pathways in human normal and leukemic stem/progenitor cells

Project description:Hypoxia inducible factors (HIF)1 and 2 are transcription factors which regulate the homeostatic response to low oxygen conditions. Since data related to the importance of HIF1 and 2 in haematopoietic stem and progenitors is conflicting, we investigated the chromatin binding profiles of HIF1 and HIF2 and linked that to transcriptional networks and the cellular metabolic state. Genome-wide ChIP-seq and transcriptome studies revealed that overlapping HIF1- and HIF2-controlled loci were highly enriched for various processes like including metabolism, particularly those involved in glucose metabolism, but also for chromatin organization, cellular response to stress and G protein-coupled receptor signaling. ChIP-qPCR validation studies confirmed that glycolysis-related genes - but not genes related to the TCA cycle or glutaminolysis - were controlled by both HIF1 and HIF2 in leukemic cell lines and primary AMLs, while in healthy human CD34+ cells these loci were predominantly controlled by HIF1 but not HIF2. However, and in contrast to our initial hypotheses, CRISPR/Cas9-mediated knockout of HIF signaling did not affect growth, internal metabolite concentrations, glucose consumption or lactate production under hypoxia. These data indicate that, while HIFs exert control over glycolysis but not OxPHOS gene expression in human leukemic cells, this is not critically important for their metabolic state.

2020-02-04 | GSE123461 | GEO

Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease [Spatial Transcriptomics]

Project description:Inflammatory skin diseases are spurred by unchecked immune-epithelial circuits. However, the specific metabolic factors involved in crosstalk and their impact on the dysregulation of these two cellular components are not well understood. To better decipher the metabolic factors involved in psoriasis, we employed spatial transcriptomics (ST), a ground-breaking technology that precisely maps gene expression from histologically-intact tissue sections. These findings identify therapeutically targetable metabolic vulnerabilities in inflammatory skin disease by unveiling a remarkable coordination of metabolic processes between the epithelial and immune compartments.

2024-04-01 | GSE237771 | GEO

Generation of macrophages that are profoundly pro-remyelinating through unexpected activation cues

Project description:Excessive inflammation within the central nervous system is injurious, but an immune response is also required for its repair. Macrophages are versatile cells that adopt different properties depending upon their microenvironment. Exposing macrophages to interleukin-4 and -13 (IL4/IL13) has incurred interest for their reparative properties. Unexpectedly, while macrophages exposed to the classic pro-inflammatory signals (interferon-γ/lipopolysaccharide, IFN/LPS) killed neurons and oligodendrocytes in culture, the addition of LPS to IL4/IL13-treated macrophages profoundly elevated IL10, repair metabolites (lactate, ornithine), glucose metabolism and the oligodendrocyte-trophic heparin-binding epidermal growth factor (HBEGF); cells did not display pro-inflammatory or neurotoxic features. In mice with spinal cord demyelination, locally-applied IL4/IL13 was insufficient to alter responses beyond controls; remarkably, the LPS/IL4/IL13-treated animals significantly increased lesional phagocytic macrophages/microglia, lactate and HBEGF levels, oligodendrogenesis and remyelination. We report a remarkably reparative state of macrophages that is unexpectedly generated by the integration of pro- (LPS) and anti- (IL4/IL13) inflammatory activation cues.

2019-09-06 | PXD015021 | Pride

Lactate sensing drives fungal immune evasion

Project description:Experiment Description RNA sequencing was performed on Candida albicans wild type cells (SC5314) grown to exponential phase on YNB Lactate, YNB Glucose, or YNB Glucose plus Lactate, and compared to exponential Candida albicans crz1 cells grown on YNB Glucose or YNB Glucose plus Lactate. Three independent experiments were performed.

2016-10-03 | E-MTAB-4579 | biostudies-arrayexpress

Harnessing the benefits of neuroinflammation: Generation of macrophages/microglia with remarkable remyelinating properties

2019-10-02 | GSE138263 | GEO

DNA methylation signature in monozygotic twins discordant for psoriatic disease [methylation array]

Project description:Psoriatic disease is a multifactorial inflammatory condition spanning from skin and nail psoriasis (Pso) to spine and joint involvement characterizing psoriatic arthritis (PsA). Monozygotic twins provide a model to investigate genetic, early life environmental exposure and stochastic influences to complex diseases, mainly mediated by epigenetics. We performed a genome-wide DNA methylation study on whole blood of monozygotic twins from 7 pairs discordant for Pso/PsA using the Infinium Methylation EPIC array (Illumina). MeDiP – qPCR was used to confirm specific signals. Data were replicated in an independent cohort of 7 patients with Pso/PsA and 3 healthy controls. We identified 2,564 differentially methylated positions between psoriatic disease and controls, corresponding to 1,703 genes, 59% within gene bodies. There were 19 regions with at least two DMPs within 1 kb of distance and significant within-pair Δβ-values (p<0.005), among them SNX25, BRG1 and SMAD3 genes, all involved in TGF-β signaling pathway, were identified. Co-expression analyses on transcriptome data identified IL-6/JAK/STAT3 and TNF-alpha pathways as important signaling axes involved in the disease, and they also suggested an altered glucose metabolism in patients’ immune cells, characteristic of pro-inflammatory T lymphocytes. The study suggests the presence of an epigenetic signature in affected individuals, pointing to genes involved in immunological and inflammatory responses. This result is also supported by transcriptome data, that altogether suggest a higher activation state of the immune system, that could promote the disease status.

2021-12-15 | GSE186713 | GEO

Hexokinase 2 and lactate mediated gene expression via histone H3 lysine 18 lactylation (CHO RNA-Seq)

Project description:Hexokinase catalyzes the first committed step in glucose metabolism by phosphorylating glucose to produce glucose-6-phosphate. Highly glycolytic proliferating cells such as cancer cells take advantage of HK2 expression to accelerate glucose metabolism even in the presence of oxygen. This acceleration not only provides sufficient glycolytic intermediates to support the anabolic demands of the cells but also inevitably accompanies increased formation of metabolic end products such as lactate. Currently, the effect of lactate caused by HK2-mediated metabolic alteration is largely unknown. A recent study found that lactate plays a role in an epigenetic alteration known as histone lactylation. Here, using RNA-seq and CUT&Tag chromatin profiling, we study the effect of HK2 and lactate on gene expression via histone lactylation (H3K18la).

2023-05-05 | GSE229153 | GEO

Hexokinase 2 and lactate mediated gene expression via histone H3 lysine 18 lactylation (CHO CUT&Tag)

2023-05-05 | GSE229151 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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