Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Liver ILC2s suppress gluconeogenesis and limit blood glucose elevation through IL-13 signaling [scRNA-seq_Hepatocyte]

ABSTRACT: The liver stores glycogen and releases blood glucose and is therefore essential for glucose metabolism. Group 2 innate lymphoid cells (ILC2s) in adipose and pancreatic tissues are involved in glucose homeostasis, but the metabolic contribution of liver ILC2s remains unclear. Herein, we show that interleukin (IL)-33 treatment induced IL-13 production in liver ILC2s, which consequently reduced blood glucose levels. IL-13 also directly suppressed gluconeogenesis in primary hepatocytes. Single-cell RNA sequencing (scRNA-seq) and cell-cell interaction analysis in liver ILC2s and hepatocytes demonstrated that IL-33 administration suppressed gluconeogenesis in a specific Hnf4a/G6pchigh-hepatocyte cluster involving expression of Stat3, which significantly interacted with liver ILC2s via IL-13/IL-13 receptor signaling. To address the regulatory mechanism underlying IL-13 production in liver ILC2s, we performed GATA3 transcriptional complex analysis, and GATA3-ChIP-seq, ATAC-seq, and scRNA-seq trajectory analyses, focusing on GATA3-interacting proteins that were functionally specific in ILC2s. AP-1 family members were found to suppress the induction of IL-13 in liver ILC2s. Thus, our study revealed a novel role for liver ILC2s in glucose homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE189286 | GEO | 2022/07/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Liver ILC2s suppress gluconeogenesis and limit blood glucose elevation through IL-13 signaling [scRNA-seq_ILC2]

Project description:The liver stores glycogen and releases blood glucose and is therefore essential for glucose metabolism. Group 2 innate lymphoid cells (ILC2s) in adipose and pancreatic tissues are involved in glucose homeostasis, but the metabolic contribution of liver ILC2s remains unclear. Herein, we show that interleukin (IL)-33 treatment induced IL-13 production in liver ILC2s, which consequently reduced blood glucose levels. IL-13 also directly suppressed gluconeogenesis in primary hepatocytes. Single-cell RNA sequencing (scRNA-seq) and cell-cell interaction analysis in liver ILC2s and hepatocytes demonstrated that IL-33 administration suppressed gluconeogenesis in a specific Hnf4a/G6pchigh-hepatocyte cluster involving expression of Stat3, which significantly interacted with liver ILC2s via IL-13/IL-13 receptor signaling. To address the regulatory mechanism underlying IL-13 production in liver ILC2s, we performed GATA3 transcriptional complex analysis, and GATA3-ChIP-seq, ATAC-seq, and scRNA-seq trajectory analyses, focusing on GATA3-interacting proteins that were functionally specific in ILC2s. AP-1 family members were found to suppress the induction of IL-13 in liver ILC2s. Thus, our study revealed a novel role for liver ILC2s in glucose homeostasis.

2022-07-27 | GSE189285 | GEO

Liver ILC2s suppress gluconeogenesis and limit blood glucose elevation through IL-13 signaling [ChIP-Seq]

2022-07-27 | GSE189284 | GEO

Liver ILC2s suppress gluconeogenesis and limit blood glucose elevation through IL-13 signaling [ATAC-Seq]

2022-07-27 | GSE189283 | GEO

Liver ILC2s suppress gluconeogenesis and limit blood glucose elevation through IL-13 signaling [bulkRNA-seq_Hepatocyte]

2022-07-27 | GSE189282 | GEO

Proteome of group 2 innate lymphoid cells (ILC2s) stimulated with IL33 and TL1A

Project description:We analyzed the total proteome of group 2 innate lymphoid cells (ILC2s) after different stimulation with interleukin-33 (IL-33), a cytokine playing a critical role in human asthma, and TL1A, a TNF-family cytokine also known to activate ILC2s. Upon combined stimulation with IL-33 plus TL1A, we show that lung ILC2s produce high amounts of IL-9 and acquire a transient ‘ILC9’ phenotype. This phenotype is characterized by simultaneous production of large amounts of type 2 cytokines (IL-5, IL-13 and IL-9), induction of the IL-2 receptor CD25 (Il2ra), and of the transcription factors IRF4, JunB and BATF, that form immune-specific complexes known to induce IL-9 expression.

2024-03-05 | PXD041987 | Pride

Specification of innate type-2 lymphocytes by the transcriptional determinant Gfi1

Project description:Innate type-2 lymphoid cells (ILC2s) function in immune responses against helminth parasites and are implicated in allergic inflammation and asthma. ILC2s are activated by the epithelial-derived cytokines IL-33 and IL-25 and are major sources of the type-2 cytokines IL-5 and IL-13. We show that the transcription factor Gfi1 promotes the generation of ILC2s and controls their responsiveness during Nippostrongylus brasiliensis infection as well as IL-33- or IL-25-instigated inflammation. Gfi1 directly activates Il1rl1, which encodes the IL-33 receptor. IL- 33 signaling upregulates Gfi1, thereby constituting a positive feedback loop that enables rapid and robust expansion of ILC2s in response to IL-33 signaling. Loss of Gfi1 in activated ILC2s results in an unusual effector state involving derepression of the IL-17 inflammatory program and co-expression of IL-13 with IL-17. ChIPseq reveals key Gfi1 targeted genes that are activated or repressed to maintain ILC2 identity. We propose that Gfi1 functions as a shared determinant within innate and adaptive immune cells to specify type-2 responses, while actively repressing the IL-17 effector state. ILC2s (~3 x 10^7 cells) were sorted from the MLN of IL-25-treated mice. Chromatin fragments bound by Gfi1 were subject to ChIP using Gfi1 antibodies and followed by high-throughput sequencing.

2013-09-13 | E-GEOD-50806 | biostudies-arrayexpress

Gene expression data of naïve wildtype and IL-33 knockout ILC2s isolated from adult male mouse lungs

Project description:Group 2 innate lymphoid cells (ILC2s) in mouse lungs are activated by the epithelium-derived alarmin IL-33. Activated ILC2s proliferate and produce IL-5 and IL-13 that drive allergic responses. In neonatal lungs, IL-33 is spontaneously released resulting in activation of lung ILC2s. Here we report that neonatal lung ILC2 activation has significant effects on ILC2 functions in adulthood. Most neonatal lung ILC2s incorporated bromodeoxyuridine (BrdU) and persisted into adulthood. BrdU+ ILC2s in adult lungs responded more intensely to IL-33 treatment than BrdU- ILC2s. In IL-33 deficient (KO) mice, lung ILC2s develop normally but they are not activated in the neonatal period. Lung ILC2s in KO mice responded less intensely to IL-33 in adulthood compared to wild type (WT) ILC2s. While there was no difference in the number of lung ILC2s, there were fewer IL-13+ ILC2s in IL-33KO than IL-33WT mice. The impaired responsiveness of ILC2s in KO mice was reversed by intranasal injections of IL-33 in the neonatal period. These results suggest that activation of lung ILC2s by endogenous IL-33 in the neonatal period may “train” ILC2s seeding the lung after birth to become long-lasting resident cells that respond more efficiently to challenges later in life.

2020-04-14 | GSE148545 | GEO

Gene expression data of naïve postnatal day 10 neonatal, naïve adult, and IL-33-activated adult ILC2s isolated from mouse lungs

2020-04-14 | GSE148539 | GEO

RNA-Seq analysis of mouse group 2 innate lymphoid cells (ILC2s) cultured with IL-33, IFN-g, and IL-27

Project description:Purpose: We found that IFN-g and IL-27 had suppressive effects on ILC2s cultured with IL-33. The goal of this study is to clarify the expressions of RNA induced by IFN-g and IL-27 in ILC2s. Methods: ILC2s were isolated from fat-asociated lymphid clusters (FALC) of wild-type mice. They were cultured with IL-33 (10ng/ml), IL-33 + IFN-g (10ng/ml), or IL-33 + IL-27 (10ng/ml) for 48hrs. RNA was isolated by Allprep DNA/RNA Micro Kit (QIAGEN), and cDNA libraries were prepared by TruSeq RNA Sample Preparation kits v2 (Illumina) according to the manufacturerâs low sample protocol. A HiSeq 1500 system (Illumina) was used for 50 single-end bases (50SE)ãsequencing. Results: Sequenced reads were trimmed for adaptor sequence, and masked for low-complexity or low-quality sequence, then mapped to the reference genome (mm9) using Bowtie2 v2.1.0 and TopHat2 v2.0.8. The transcript abundances were estimated as FPKM (fragments per kilobase of exon million fragments mapped) value using Cufflinks v2.1.1. We found that both IL-27 and IFN-g upregulated the expression of STAT1 and IRF1 which are regulated downstream of IFN-g receptor signaling, but there was no difference in the expression of GATA3, a critical transcription factor for ILC2 functions. Conclusions: Our study represents the detailed differences of RNA expressions by RNA-seq technology. RNA-Seq analysis of ILC2s cultured with IL-33 (10ng/ml), IL-33 + IFN-g (10ng/ml), or IL-33 + IL-27 (10ng/ml) for 48hrs.

2015-10-30 | E-GEOD-73272 | biostudies-arrayexpress

Specification of innate type-2 lymphocytes by the transcriptional determinant Gfi1

2013-09-13 | GSE50806 | 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