Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Kidney GATA3+ regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury

ABSTRACT: FoxP3+ regulatory T cells (Tregs) play crucial roles in peripheral immune tolerance. In addition, Tregs that reside or accumulate in nonlymphoid tissues, called tissue Tregs, exhibit tissue-specific functions and contribute to the maintenance of tissue homeostasis and repair. In an experimental mouse model of crescentic glomerulonephritis induced by an anti-glomerular basement membrane antibody, Tregs started to accumulate in the kidney on day 10 of disease onset and remained at high levels (~30–35% of CD4+ T cells) during the late stage (days 21–90), which correlated with stable disease control. Treg depletion on day 21 resulted in the relapse of renal dysfunction and an increase in Th1 cells, suggesting that Tregs are essential for disease control during the convalescence stage. The Tregs that accumulated in the kidney showed tissue Treg phenotypes, including high expression of GATA3, ST2 (the IL33 receptor subunit), amphiregulin (Areg), and PPARγ. Although T-bet+ Tregs and RORγt+ Tregs were observed in the kidney, GATA3+ Tregs were predominant during the convalescence stage, and a PPARγ agonist enhanced the accumulation of GATA3+ Tregs in the kidney. To understand the function of specific genes in kidney Tregs, we developed a novel T cell transfer system to T cell-deficient mice. This experiment demonstrates that ST2, Areg, and CCR4 in Tregs play important roles in the accumulation of GATA3+ Tregs in the kidney and in the amelioration of renal injury. Our data suggest that GATA3 is important for the recruitment of Tregs into the kidney, which is necessary for convalescence after renal tissue destruction.

ORGANISM(S): Mus musculus

PROVIDER: GSE159420 | GEO | 2020/10/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ST2+ T-regulatory Cells in Renal Inflammation and Fibrosis following Ischemic Kidney Injury

Project description:The role of IL-33 and its receptor ST2 in kidney injury is not well understood. This study demonstrates the importance of ST2 expression on the T-regulatory cells (Tregs) for the resolution of renal injury by suppressing inflammation and fibrosis. Treg-specific deletion of ST2, detrimentally impacted late outcomes of renal injury worsening the impairment of kidney function, inflammation, and fibrosis.

2024-08-27 | GSE272380 | GEO

Kidney GATA3+ regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury

Project description:Kidney GATA3+ regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury

| PRJNA668850 | ENA

Transcriptional profiling of mouse ST2+ and ST2- Tregs across tissues

Project description:Foxp3+ regulatory T cells (Tregs) are critical mediators of peripheral tolerance and immune homeostasis. Tregs that express the IL-33 receptor ST2 are enriched in peripheral nonlymphoid tissues and can exert a variety of tissue-specific functions from metabolic regulation within adipose tissue to skeletal muscle repair. However, the relationship between ST2+ and ST2- Tregs within and across different tissues remains unclear. To compare murine ST2- and ST2+ Tregs within and across tissues, we performed RNA sequencing (RNAseq) of ST2-CD44hi and ST2+CD44hi Tregs from blood, spleen, lungs, visceral adipose tissue (VAT), colon, and skin. RNAseq was also performed on ST2- CD44lo CD62L+ Tregs from the spleen and lungs. We found that the tissue microenvironment was the major factor shaping the transcriptome of Tregs across tissues. Across the tissues studied, Treg transcriptomes displayed an ordered hierarchy that may represent graded levels of activation or differentiation across tissues. We also identified a core signature that distinguished ST2+ Tregs from ST2- Tregs across tissues and a large number of differentially expressed genes between ST2- and ST2+ Tregs within individual tissues that could support the tissue-specific adaptation and function of ST2+ Tregs. In summary, our work highlights the unique, tissue-specific phenotype of ST2+ Tregs and reveals a core ST2+ Treg transcriptional signature shared across tissues.

2022-07-24 | GSE182322 | GEO

Single-cell expression profiling of visceral adipose tissue and splenic CD4+ T cells from Treg-bmal1WT and Treg-bmal1KO mice at ZT0 and ZT12.

Project description:we reported single-cell gene expression of CD4+ T cells from the visceral adipose tissue of from male Foxp3-Cre.YFP bmal1WT or Foxp3-Cre.YFP bmal1flox/flox mice, and from spleen from bmal1WT mice, at ZT0 or ZT12. We found that VAT Tregs could be subdivided into five subtypes: p1 ST2+, p2 ST2+, Tbet+, IL18r+ and resting clusters. We found diurnal variation within the ST2+ subgroups, where the more activated p1 ST2+ Tregs were more represented at ZT0 in WT VAT Tregs. Such variations were not observed in splenic Tregs. In contrast, bmal1KO VAT Tregs were were enriched in the ST2+ Tregs, and had a constitutively high proportion of the p1 ST2+ subtype at ZT0 and ZT12.

2022-07-28 | GSE206949 | GEO

RNA-seq profile of expanded human ST2-transduced Tregs cultured with IL-2 and TCR in the presence or absence of IL-33

Project description:Because of the extensive data in mice supporting the concept that ST2+ Tregs might have desirable therapeutic properties, including tissue repair function, high suppressive capacity, and enhanced stability, we engineered human blood Tregs to constitutively express ST2 (IL-33R). Here we used RNA sequencing to explore the effects of short-term culture with IL-33 on human ST2-transduced Tregs.

2019-02-04 | GSE117481 | GEO

The Protective Role of Integrin α4β7 and Amphiregulin-Expressing Innate Lymphoid Cells in Lupus Nephritis

Project description:Type-2 innate lymphoid cells (ILC2s) have emerged as key immune-response regulators in renal-inflammatory diseases such as lupus nephritis. However, the adhesion and migration of ILC2s, including in the homeostatic and diseased kidney, are poorly understood. By integrating transcriptomic profiling, flow cytometry, live-cell imaging, and in-vivo models, we showed that renal ILCs are retained in the homeostatic kidney by the adherence of their cell-surface integrin α4β7 to VCAM-1, E-cadherin or fibronectin on structural kidney cells. When cultured on these ligands, ILC2s demonstrated remarkable migration. Knocking down integrin-α4β7 expression reduced ILC2 Areg production. In lupus nephritis, TLR7/9 may downregulate ILC2 expression of integrin-α4β7, thereby both reducing Areg expression and promoting ILC2 egress. Areg loss may promote the proinflammatory-cytokine secretion by T cells. IL-33 upregulated ILC2 integrin-α4β7 and Areg expression. Notably, IL-33 treatment enhanced survival in lupus nephritis by mitigating kidney inflammation. Thus, ILC2 adhesion may be a therapeutic target for autoimmune kidney diseases.

2024-05-16 | GSE234742 | GEO

ST2+ T-regulatory Cells in Renal Inflammation and Fibrosis following Ischemic Kidney Injury

Project description:Here, we delineated the role of the ST2 specifically in Treg cells, using murine renal injury models and kidney organoids.

2024-08-27 | GSE224295 | GEO

Metabolic control in VAT by Tregs through OSM-mediated suppression of adipogenesis

Project description:Regulatory T cells (Tregs) play diverse roles in tissue homeostasis. In visceral adipose tissue (VAT), resident Tregs, enriched with PPARγ, are clonally expanded in a IL-33 dependent manner. However, the tissue-specific functions of VAT Tregs, with unique transcriptome compared to spleen or other peripheral tissues, remain largely unknown. We identified two PPARγ+ mesenchymal stromal cells in VAT (VmSCs), named VmSC4s (PPARγ+Thy1-) and 5s (PPARγ+Thy1+). Lineage-tracing and transcriptome analysis revealled that VmSC4s contain precursors for VmSC5s. We also demonstrated that VAT Tregs directly suppress adipogenic differentation of VmSC5s through Oncostain M (OSM) to promote insulin sensitivity and glucose tolerance. Thus, VAT-Treg-derived OSM and VmSCs-displayed OSMR maintain tissue homeostasis via limiting the differentiation of dysfunctional adipocytes, which provide therapeutic targets for treating obesity and diabetes.

2023-08-01 | GSE226889 | GEO

Pairwise comparison of ST2+ and ST2- FOXP3+ T cells derived from mouse intestinal tumors

Project description:Colorectal cancer (CRC) was induced in Foxp3/eGFP reporter mice by the azoxymethane/dextran sulphate sodium salt (AOM/DSS) protocol. Mice were injected i.p. with the procarcinogen AOM (12.5 mg/kg of body weight). After 1 week, mice received drinking water supplemented with 2.5% DSS for 5 to 7 days, followed by 2 weeks of regular water. The DSS administration was repeated twice with 2% DSS. Mice were sacrificed at week 11 and lamina propia lymphocytes (LPLs) from the colon were isolated. CD4+FOXP3+ (eGFP+) ST2+ or ST2- Tregs were separated from colonic LPLs of CRC induced mice using a FACSAria II cell sorter. Microarray analysis was performed to analyze if ST2+ FOXP3+ Tregs from the colon of CRC mice present a distinct transcription pattern compared to ST2- FOXP3+ Tregs. By this, the role of ST2 for Treg function during intestinal tumorigenesis should be characterized.

2019-05-31 | E-MTAB-6842 | biostudies-arrayexpress

PPARs and c-Myc regulate metabolism of renal tubules

Project description:Different segments of renal tubules have distinct metabolic features and functions, and defective metabolism in renal tubules is involved in the pathobiology of kidney diseases. However, the mechanisms underlying the metabolic regulation in renal tubules remain to be defined. We demonstrated that the renal proximal tubule (PT) has high expression of fatty acid and lipid metabolism enzymes, which is transcriptionally upregulated by abundantly expressed peroxisome proliferator-activated receptor (PPAR)/γ to support active lipid metabolism. In contrast, the renal distal tubule (DT) has elevated glycolytic enzyme expression corresponding with high rates of glycolysis, and this increased expression is mediated by abundantly expressed c-Myc. In addition, Nrf2 upregulated glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-dependent malic enzyme 1 expression for NADPH production and antioxidation in the DT. Highly expressed PPARγ transcriptionally enhanced expression of the protease iRhom2 in the PT, which suppressed epidermal growth factor (EGF) expression and secretion, inhibiting EGF receptor activation-dependent glycolytic gene expression and maintaining the low level of glycolysis. PPARγ inhibition reduced iRhom2 expression and increased EGF and GLUT1 expression in the PT in mice, resulting in hypertrophy of renal tubules and inhibited kidney functions, which can be rescued by inhibition of glycolysis via treatment with 2-deoxy-D-glucose. These findings delineate instrumental molecular mechanisms underlying the active lipid metabolism and suppressed glycolysis in the PT and active glycolysis in the DT and reveal critical roles for PPARs and c-Myc in maintaining metabolic homeostasis in the kidney

2018-11-15 | PXD007828 | 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