Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Traf2 and Traf3 B cell knockout mice and Baff tg mice - gene expression in lymph node B cells

ABSTRACT: Tumor necrosis factor-associated factors 2 and 3 (TRAF2 and TRAF3) were shown to function in a co-operative and non-redundant manner to suppress nuclear factor-κB2 (NF-κB2) activation, gene expression and survival in mature B cells. In the absence of this suppressive activity, B cells developed independently of the obligatory B cell survival factor, BAFF (B cell activating factor of the tumor necrosis factor family). This constitutive, lineage-specific suppression of B cell survival by TRAF2 and TRAF3 determines the requirement for BAFF to sustain B cell development in vivo. We wished to investigate the effect on gene expression in B cells which lacked the negative regulators TRAF2 and TRAF3, and hence had hyperactive NF-kB2 signalling. As Baff-tg mice display a similar phenotype, and have a genetic modification which acts in the same pathway, yet further up, than TRAF2 and TRAF3, we wished to compare and contrast Baff-tg B cells with TRAF2 and TRAF3 deficient B cells. This analysis should identify genes that are important in B cell survival. Keywords: Genetic modification

ORGANISM(S): Mus musculus

PROVIDER: GSE10422 | GEO | 2008/02/28

SECONDARY ACCESSION(S): PRJNA108073

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of mouse lymph node derived B cells from Traf2 and Traf3 B cell knockout mice and Baff tg mice

Project description:Tumor necrosis factor-associated factors 2 and 3 (TRAF2 and TRAF3) were shown to function in a co-operative and non-redundant manner to suppress nuclear factor-ÎºB2 (NF-ÎºB2) activation, gene expression and survival in mature B cells. In the absence of this suppressive activity, B cells developed independently of the obligatory B cell survival factor, BAFF (B cell activating factor of the tumor necrosis factor family). This constitutive, lineage-specific suppression of B cell survival by TRAF2 and TRAF3 determines the requirement for BAFF to sustain B cell development in vivo. We wished to investigate the effect on gene expression in B cells which lacked the negative regulators TRAF2 and TRAF3, and hence had hyperactive NF-kB2 signalling. As Baff-tg mice display a similar phenotype, and have a genetic modification which acts in the same pathway, yet further up, than TRAF2 and TRAF3, we wished to compare and contrast Baff-tg B cells with TRAF2 and TRAF3 deficient B cells. This analysis should identify genes that are important in B cell survival. Experiment Overall Design: Lymph node B cells were purified from Traf2 B cell knockout mice, Traf3 B cell knockout mice, Baff-tg mice and respective controls. RNA was extracted and hybridised to Affymetrix 430 2.0 Mouse Genome Arrays. Samples were processed and hence analysed on three spearate days. Day 1 two control mice: Traf2lox/lox pool and CD19-cretg were compared to two knockout mice: Traf2DB 80 and Traf3DB 94. On Day 2 three control mice: Traf2lox/lox 77, Traf2lox/lox 79 and Traf3lox/lox 97 were compared to two knockout mice: Traf2DB 76 and Traf3DB 01. On Day 3 three control mice: WT33, WT34, WT35 were compared to three Baff-tg mice: Baff-tg 99, Baff-tg 100, Baff-tg 101.

2008-04-07 | E-GEOD-10422 | biostudies-arrayexpress

Mus musculus

Project description:Traf2 and Traf3 B cell knockout mice and Baff tg mice - gene expression in lymph node B cells

| PRJNA108073 | ENA

Tumor Necrosis Factor Associated Factor 2 Mediates Cardiac Protection Through Non-canonical NF-κB Signaling

Project description:To elucidate the mechanisms responsible for cytoprotective effects of tumor necrosis factor receptor activated factor 2 (TRAF2) in the heart, we employed genetic gain and loss of function studies ex vivo and in vivo in mice with cardiac restricted overexpression of TRAF2 (Myh6-TRAF2LC). Crossing Myh6-TRAF2LC mice with mice lacking canonical signaling (Myh6-TRAF2LC/Myh6-IκBαΔN) abrogated the cytoprotective effects of TRAF2 ex vivo. In contrast, inhibiting the JAK/STAT pathway did not abrogate the cytoprotective effects of TRAF2. Transcriptional profiling of wild-type, Myh6-TRAF2LC, Myh6-TRAF2LC/Myh6-IκBαΔN hearts suggested that the non-canonical NF-κB signaling pathway was upregulated in the Myh6-TRAF2LC hearts. Western blotting and ELISA for the NF-κB family proteins p50, p65, p52 and RelB on nuclear and cytoplasmic extracts from naïve 12 week old wild-type, Myh6-TRAF2LC and Myh6-TRAF2LC/Myh6-IκBαΔN mouse hearts showed increased expression levels and increased DNA binding of p52 and RelB, which are NF-κB family members, whereas there was no increase in expression nor DNA binding of the p50 and p65 subunits. Crossing Myh6-TRAF2LCmice with RelB-/+mice (Myh6-TRAF2LC/RelB-/+) attenuated the cytoprotective effects of TRAF2 ex vivo and in vivo. Viewed together, these results suggest that cross-talk between the canonical and non-canonical NF-κB signaling pathways is required for mediating the cytoprotective effects of TRAF2.

2017-12-15 | GSE107668 | GEO

Expression data from U-87 human glioma cells with proficient and deficient NF-кB after treatment with temozolomide

Project description:The transcription factor, NF-кB, plays a central role in the response to DNA damage. This ubiquitous family of proteins is made up of five subunits: p50 (NF-κB1, p105), p52 (NF-κB2, p100), p65 (relA), relB, and crel that appear in their mature form as dimers. Following stimulation, NF-κB dimers translocate to the nucleus where they bind specific consensus elements (κB-sites) in the promoter region of genes involved in cell survival, inflammation and the immune system. While there is a general propensity of NF-кB to mediate survival, this is not always the case and several reports note the pro-apoptotic nature of the NF-кB pathway. In examining the NF-кB response to DNA damage, we have found that the p50 subunit plays a central role in modulating cytotoxicity following TMZ treatment in malignant glioma. In the current study, given the importance of p50 to the cytotoxic response to TMZ, we set out to identify NF-кB-dependent factors that modulate the response to TMZ. U-87 glioma cells stably transfected with either control-shRNA or p105-shRNA and subsequently treated with temozolomide (TMZ) were selected for RNA extraction and hybridization on Affymetrix microarrays. Each category contains 3 biologic replicates.

2015-01-29 | E-GEOD-65363 | biostudies-arrayexpress

Transcriptional responses of mantle cell lymphoma (MCL) after NIK knockdown

Project description:MCL lines were treated with or without 100ng/ml doxycycline for 7 days This experiment is designed to see if shRNA-mediated knockdown of NIK downregulates NFKB signaling in MCL lines with mutations in upstream regulators of the alternative pathway (TRAF2 & TRAF3)

2013-12-01 | GSE52435 | GEO

RNAseq data from in vitro-stimulated (6 hours) murine nfkb2fl/flCD19-Cre and CD19-Cre splenic B cells purified by magnetic cell separation (BAFF)

Project description:RNAseq analysis of BAFF in vitro-stimulated (6 hours) murine nfkb2fl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor NF-kB2 in BAFF-stimulated B cells.

2016-02-01 | GSE75761 | GEO

YTHDF2-m6A-NF-kB axis controls anti-tumor immunity through regulating intratumoral Treg survival and function [RNA-seq]

Project description:N6-methyladenosine (m6A) in messenger RNA (mRNA) regulates immune cells in homeostasis and in response to infection and inflammation. The function of YTHDF2 in the tumor microenvironment (TME) in these contexts has not been explored. We discovered that loss of Ythdf2 in regulatory T (Treg) cells can reduce tumor growth in mice while maintaining peripheral homeostasis. In the tumor microenvironment, Ythdf2-deficient Treg cells have impaired function and poor survival. The elevated tumor necrosis factor (TNF) signaling in the TME grants the location-specific function of YTHDF2, which participates in the feedback regulation of NF-kB signaling by accelerating the degradation of m6A-modified, NF-kB negative regulators, Nlrc3, Nfkbie, and Traf3. TME-specific regulation of Treg by YTHDF2 points to YTHDF2 as a target for anti-cancer immunotherapy, where intratumoral Treg cells can be targeted to enhance antitumor immune response, while avoiding Treg cells in the periphery to minimize undesired inflammations.

2023-06-07 | GSE216959 | GEO

YTHDF2-m6A-NF-kB axis controls anti-tumor immunity through regulating intratumoral Treg survival and function [RIP-seq]

2023-06-07 | GSE216958 | GEO

YTHDF2-m6A-NF-kB axis controls anti-tumor immunity through regulating intratumoral Treg survival and function

2023-06-07 | GSE230418 | GEO

TRAF3 loss-of-function Reveals the Non-Canonical NF-κB Pathway as a Therapeutic Target in Diffuse Large B-cell Lymphoma

Project description:Treatment of diffuse large B-cell lymphoma (DLBCL) remains challenging due to extensive molecular, clinical, and pathological heterogeneity. Here, we report recurrent focal deletions of the chr14q32.31-32 locus, including TRAF3, a negative regulator of NF-κB signaling, in a cohort of uniformly-treated de novo DLBCL (24/324 cases). Integrative analysis uncovered a correlation between TRAF3 copy number loss and TRAF3 reduced expression. CRISPR-mediated TRAF3 loss-of-function (LOF) in DLBCL cell lines enhanced non-canonical NF-κB (NC NF-κB) signaling, rendering cells sensitive to shRNA-induced knockdown of the central NC NF-κB kinase, NIK. NIK pharmacological inhibitors differentially impaired proliferation, and induced apoptosis of TRAF3 LOF cells, further suggesting an acquired onco-addiction to NC NF-κB. Beyond these cell-intrinsic effects, co-culturing of TRAF3 LOF DLBCL cells with primary human CD8+ T-cells revealed an impairment in effector marker induction (Granzyme B, IFNγ) and proliferation in the latter. Accordingly, a reduction in T-cell infiltrates was observed in the microenvironment of TRAF3-low expressing primary DLBCL tumor samples. Neutralization of IL10 produced by TRAF3 LOF cells restored and enhanced GZMB and IFNγ expression in co-cultured CD8+ T-cells. Our findings demonstrate a direct relationship between TRAF3 genetic alterations and NC NF-κB activation, favoring pro-oncogenic cell-intrinsic effects and immune-evasive mechanisms, and highlight NIK as a therapeutic target in defined subset of DLBCL.

2024-04-11 | GSE218750 | 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