Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tlr9 deficiency in B cells leads to obesity by modulating the immune system and gut microbiota

ABSTRACT: We generate B-cell-specific Tlr9-deficient (Tlr9fl/fl/Cd19Cre+/-, KO) B6 mice and model obesity using a high-fat diet. Compared with control mice, B cell Tlr9-deficient mice exhibited increased weight gain, impaired glucose and insulin tolerance, reduced IL-10-producing B cells and increased inflammation in fat tissues. Tlr9 deficiency affected B cell differentiation, immunoglobulin levels, and T cell subsets. Furthermore, altered gut microbiota in B-cell-specific Tlr9-deficient mice led to a pro-inflammatory status in gut associated lymphoid tissues and glucose metabolism dysregulation. Using 16S rRNA sequencing we report altered gut microbial communities in the KO mice. Indeed, a reduction in Lachnospiraceae, may play a key role in the observed metabolic phenotypes in KO mice. Also, We identify an important network involving Tlr9, Irf4 and Il-10.

ORGANISM(S): Mus musculus

PROVIDER: GSE263396 | GEO | 2024/04/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Galectin-3 Deficiency Exacerbates Hyperglycemia and the Endothelial Response to Diabetes

Project description:Microarray analyses were performed in order to determine the effect of galectin-3 ablation on the endothelial transcriptional response in a mouse model of type 2 diabetes. Galectin-3-deficient mice (KO) and wild-type C57BL/6 (WT) were fed a high-fat diet (60% fat calories) or standard chow for 8 weeks. CD105+/CD45- endothelial cells were isolated from the aortae and skeletal muscles of these mice by FACS. Whole genome microarray expression profiling revealed greater transcriptional dysregulation in the endothelium of the KO after high-fat feeding compared to WT. Transcripts dysregulated in the KO endothelium after HFD include those involved in glucose uptake and insulin signaling, oxidative stress, vasoregulation, coagulation, and atherogenesis. Real-time PCR confirmed transcriptional downregulation of the glucose transporter, Glut4, and immunofluorescence staining confirmed reduced GLUT4 protein in the endothelium and mudcle of the KO compared to WT. The transcriptional and histological data was consistent with physiological studies showing exacerbated hyperglycemia and coagulation in the KO. These results suggest that galectin-3 serves a protective role against metabolic dysregulation and endothelial dysfunction in diabetes. Galectin-3-deficient mice (KO) and wild-type C57BL/6 (WT) were fed either a high-fat diet (60% fat calories) or standard chow diet (12% fat calories) for 8 weeks. Three independent experiments were performed. For each experiment, the aorta and skeletal muscle from 3-4 animals per diet/genotype group were excised and pooled for each tissue. Live, CD105+/CD45- endothelial cells were isolated from the aortic and muscle suspensions by FACS.

2015-08-01 | E-GEOD-57329 | biostudies-arrayexpress

Cell intrinsic expression of TLR9 in autoreactive B cells constrains BCR/TLR7-dependent responses

Project description:Endosomal Toll-like receptors (TLRs) play an important role in the etiology of systemic autoimmune diseases such as SLE, where DNA- and RNA-associated autoantigens activate autoreactive B cells through TLR9- and TLR7-dependent pathways, respectively. Nevertheless, TLR9-deficient autoimmune prone mice develop more severe clinical disease, while TLR7-deficient and TLR7/9-double deficient autoimmune-prone mice develop less severe disease. To determine whether the regulatory activity of TLR9 is B cell intrinsic, we have now directly compared the functional properties of autoantigen activated WT, TLR9-deficient and TLR7-deficient B cells, in an experimental system where proliferation depends on BCR/TLR co-engagement. In vitro, TLR9-deficient cells are less dependent on survival factors for a sustained proliferative response than either WT or TLR7-deficient cells. The TLR9-deficient cells also preferentially differentiate toward the plasma cell lineage, as indicated by expression of CD138, sustained expression of IRF4, and other molecular markers of plasma cells. In vivo, autoantigen-activated TLR9-deficient cells give rise to greater numbers of autoantibody producing cells. Our results identify distinct roles for TLR7 and TLR9 in the differentiation of autoreactive B cells that explain the capacity of TLR9 to limit, and TLR7 to promote, the clinical features of SLE. AM14 WT, Tlr7-/-, Tlr9-/- and Tlr7/9-/- B cells were stimulated with PL2-3 for 0, 6, 24, and 42 hours, for a total of 16 samples.

2015-03-04 | E-GEOD-58756 | biostudies-arrayexpress

The effects of SCAP deletion on gene expression of activated B cells

Project description:To investigate the role of SREBP signaling in B cell activation, we stimulated SCAP+/+CD19Cre/+ (WT) and SCAPfl/fl CD19Cre/+ (KO) B cells with LPS, anti-CD40 or anti-IgM for 24 hrs and performed RNA sequencing to identifiy the differences.

2022-06-30 | GSE204913 | GEO

Galectin-3 Deficiency Exacerbates Hyperglycemia and the Endothelial Response to Diabetes

2015-08-01 | GSE57329 | GEO

Cell intrinsic expression of TLR9 in autoreactive B cells constrains BCR/TLR7-dependent responses

2015-03-04 | GSE58756 | GEO

Changes in endothelial cell secretome after sirtuin-1 knock-down

Project description:Sirtuin1 (Sirt1) in skeletal muscle (SK) and fat protects against metabolic damage by stimulating insulin sensitivity. Here we report that mice with selective deletion of endothelial Sirt1 (E-Sirt1-KO) paradoxically exhibit heightened whole-body insulin sensitivity. Akt phosphorylation, glucose uptake, and glycolysis are boosted in SK and brown adipose tissue (BAT) of E-Sirt1-KO mice. E-Sirt1-KO mice have higher energy expenditure and are partially protected from high-fat diet-induced insulin resistance. Enhanced insulin sensitivity and peripheral tissue Akt phosphorylation in E-Sirt1-KO mice is transferrable to wild-type mice via the systemic circulation after surgical parabiosis. Silencing of Sirt1 in endothelial cells upregulates transcription of the F-actin-binding protein thymosin beta-4 (Tβ4), whose secretion activates Akt in skeletal myotubes. Sirt1 downregulation stimulates endothelial Tβ4 transcription through inhibition of autophagy and upregulation of nuclear factor-kappa B signaling. Thus, unlike Sirt1 in skeletal muscle and fat, endothelial Sirt1 curtails whole-body insulin sensitivity by inhibiting expression of secreted Tβ4.

2023-08-07 | PXD030565 | Pride

B-cell KO mice data

Project description:Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium, and the microbiota. We found that mice lacking B lymphocytes, or lacking IgA, have low intestinal expression of lipid metabolism genes regulated by the transcription factor GATA4, and a consequent decrease in fat absorption in the intestine. The defect disappeared in germ free mice, suggesting that it is dependent on the microbiota; and sequencing analysis of the bacteria showed subtle differences between normal and B-cell deficient mice. Analysis of gene expression of gut biopsies from patients with common variable immunodeficiency and intestinal dysfunction revealed a high similarity to mouse B-cell knockout profiles. These data provide an explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans. This series represents first part of the study including: 1) B-cell KO mice of different strains and their controls 2) germ free B-cell Ko mice and their controls 3) B lymphocytes Intensity of each channel was extracted from two-color arrays. We used direct dye swap design and performed paired analysis between small intestine of KO and control mice. Corresponding pairs of KO and control were hybridized on the same array and can be matched by the array name. For comparison between B lymphocytes and intestinal tissue we used B-cell KO intestinal samples and B lymphocytes samples balancing the number of Cy5/3 labeled samples in the groups.

2011-11-15 | E-GEOD-23573 | biostudies-arrayexpress

Lachnospiraceae treatment on high fat diet fed WT and Nlrp12 ko mice

Project description:Lachnospiraceae treatment on high fat diet fed WT and Nlrp12 ko mice

| PRJEB26985 | ENA

CSE-induced hydorogen sulfide improves glucose homeostasis and inhibits beta-cell failure in high-fat diet mice

Project description:CSE knockout (CSE-KO)mice at age 6 months were fed a high fat diet (HFD) for 8 weeks.we determined the effects of CSE knockdown on beta-cell function and mass in islets from the mice. After 8 weeks of the HFD,blood glucose levels were drasically increaced in CSE-KO mice compared with WT mice. To assess the effect of HFD on gene expression in CSE-KO mice,we performed a comparative DNA microarray analysis 2 samples analysis.control is CSE-WT(HFD+)

2013-09-02 | E-GEOD-50458 | biostudies-arrayexpress

Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.

Project description:The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA-Seq. Comparing to WT mice, adiponectin KO mice exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways including glycolysis, TCA cycle, fatty-acid activation and synthesis, triglyceride synthesis and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weights comparing to WT mice. When fed a high fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the livers. These lipogenic defects are consistent with the downregulation of lipogenic genes in the KO mice.

2012-09-04 | GSE38144 | 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