Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Non-classical action of Ku70 promotes Treg suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma

ABSTRACT: To explore the role of Ku70 in Treg cell biology, we isolated conventional T cells (Tconv) and regulatory T cells (Treg) from Foxp3Yfp-cre mice and performed Ku70 ChIP-seq. Furthermore, to investigate the impact of Ku70 deficiency on Foxp3 binding patterns, we sorted Treg cells from Foxp3Cre (WT) and Xrcc6fl/fl;Foxp3Cre (KO) mice and conducted Foxp3 ChIP-seq. These analyses revealed that Ku70 forms a complex with FOXP3, which supports FOXP3 transcriptional activity.

ORGANISM(S): Mus musculus

PROVIDER: GSE278950 | GEO | 2024/11/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Effect of depletion of Ku70 on gene expression profiles of murine regulatory T cells in lung tumor microevnronment

Project description:The functions of the DNA repair protein Ku70 in immune homeostasis and tumor immunity remain unexplored. Here, we conducted deep sequencing of mRNA profiles from tumor-infiltrating Treg cells (from Foxp3Cre and Xrcc6fl/fl;Foxp3Cre mice injected with Lewis lung carcinoma cells). By comparing gene expression profiles, we found that Ku70-absent Treg displayed activated pathways in response to inflammatory factors and upregulated expression of genes negatively regulated by Foxp3. These findings strongly indicate that Ku70 plays a supportive role in enhancing Foxp3 transcriptional activity.

2024-11-04 | GSE247031 | GEO

Comparative proteomic analysis of mouse CD4+Foxp3+ regulatory T cells and CD4+Foxp3- conventional T cells

Project description:In this study, we compared the proteomes of mouse CD4+Foxp3+ regulatory T cells (Treg) and CD4+Foxp3- conventional T cells (Tconv) in order to build a data set of proteins differentially regulated in these two cell populations. The data set contains mass spectrometry results from the analysis of 7 biological replicates of Treg/Tconv cell samples purified by flow cytometry, each experiment performed from a pool of 4-5 mice. Global proteomic analysis of each sample was performed by single-run nanoLC-MS/MS, using chromatographic separation of peptides on 50cm C18 reverse-phase columns, with either a 480min gradient on LTQ-Velos orbitrap mass spectrometer (replicates 1 and 2) or a 300min gradient on Q-Exactive orbitrap mass spectrometer (replicates 3-7). Several MS injection replicates were performed for some experiments, leading to 27 raw files composing the data set. The detailed description of each analysis (file name, sample type, biological replicate number, MS technical replicate number, MS instrument used, sample name in MaxQuant ouput) is given in the table “Files list.txt”.

2017-04-10 | PXD004436 | Pride

Inverted chromatin immunoprecipitation identifies Tcf1 as a negative regulator of Foxp3 expression

Project description:Regulatory T (Treg) cells are important regulators of the immune system and have versatile functions for the homeostasis and repair of tissues. They express the forkhead box transcription factor Foxp3 as a lineage-defining protein. In mature Treg cells, the Foxp3 core promoter is unmethylated indicating that this area could harbor a transcription factor complex to initiate or repress gene expression, respectively. We used an unbiased method to identify Foxp3-promoter-binding transcription factors (TFs) by inverted chromatin immunoprecipitation (IP) followed by quantitative mass spectrometry. We identified several candidate factors which showed Foxp3-promoter suppressive capacity, one of which was T-cell factor 1 (Tcf1). Using viral overexpression and CRISPR/Cas knockout studies, we identified Tcf1 as a repressor of Foxp3 expression in primary conventional CD4 T cells (Tconv). In Tcf1-deficient animals, increased levels of Foxp3intermediateCD25negative T cells were identified in secondary lymphoid tissues, implicating that Tcf1 protects Foxp3-negative T cells from inadvertent Foxp3 expression.

2020-05-26 | PXD018764 | Pride

Two Histone/Protein Acetyltransferases, CBP and p300, Are Indispensable for Foxp3+ T-regulatory Cell Development and Function

Project description:T-regulatory (Treg) cells are important to immune homeostasis, and Treg cell deficiency or dysfunction leads to autoimmune disease. An histone/protein acetyltransferase (HAT), p300, was recently found important for Treg function and stability, but further insights into the mechanisms by which p300 or other HATs affect Treg biology are needed. Here we show that CBP, a p300 paralog, is also important in controlling Treg function and stability. Thus, while mice with Treg-specific deletion of CBP or p300 developed minimal autoimmune disease, the combined deletion of CBP and p300 led to fatal autoimmunity by 3-4 weeks of age. The effects of CBP and p300 deletion on Treg development are dose-dependent, and involve multiple mechanisms. CBP and p300 cooperate with several key Treg transcription factors that act on the Foxp3 promoter to promote Foxp3 production. CBP and p300 also act on the Foxp3 CNS2 region to maintain Treg stability in inflammatory environments by regulating pCREB function and GATA3 expression, respectively. Lastly, CBP and p300 regulate the epigenetic status and function of Foxp3. Our findings provide insights into how HATs orchestrate multiple aspects of Treg development and function, and identify overlapping but also discrete activities for p300 and CBP in control of Treg cells. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of fl-p300/Foxp3cre mice and fl-CBP/Foxp3cre, compared to wild type (Foxp3cre) control (all C57Bl/6 background).

2014-08-12 | E-GEOD-60318 | biostudies-arrayexpress

Non-classical action of Ku70 promotes Treg suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma

Project description:Non-classical action of Ku70 promotes Treg suppressive function through a FOXP3-dependent mechanism in lung adenocarcinoma

| PRJNA1169822 | ENA

Inhibition of p300 impairs Foxp3+ T-regulatory cell function and promotes anti-tumor immunity

Project description:Foxp3+ T-regulatory (Treg) cells maintain immune homeostasis and limit autoimmunity, but can also curtail host responses to cancers. Tregs are therefore promising targets to enhance anti-tumor immunity. Histone/protein acetyltransferases (HATs) promote chromatin accessibility, gene transcription and the function of multiple transcription factors and non-histone proteins. We found that conditional deletion or pharmacologic inhibition of one specific HAT, p300, in Foxp3+ Tregs, increased TCR-induced apoptosis in Tregs, impaired Treg suppressive function and iTreg peripheral conversion, and limited tumor growth in immunocompetent, but not in immunodeficient, hosts. Our data demonstrate that p300 is important for Foxp3+ Treg function and homeostasis in vivo and in vitro, and identify a novel mechanism to diminish Treg function without overtly impairing effector Tcell responses or inducing autoimmunity. Collectively, these data suggest a new approach for cancer immunotherapy. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of fl-p300/Foxp3cre mice, compared to wild type (Foxp3cre) control (all C57Bl/6 background).

2013-08-18 | E-GEOD-47989 | biostudies-arrayexpress

Expression Data of Treg and Tconv Cells from FoxP3-GFP Chimeric and FoxP3-ires-GFP B6 and NOD Mice

Project description:The aim of this study was to quantify the impact of chimeric Foxp3-GFP protein on the Treg cell transcriptional program. Duplicate samples of Tconv (CD3+CD4+GFP-) and Treg (CD3+CD4+GFP+) splenocytes were double-sorted to achieve > 99.0% purity, from 6 weeks old male Foxp3-Fusion-GFP and Foxp3-ires-GFP mice of both B6 and NOD backgrounds. Following cell sorting into Trizol, RNA was purified, labeled and hybridized to Affymetrix arrays.

2012-04-26 | E-GEOD-37605 | biostudies-arrayexpress

Comparison of expression profiles of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells

Project description:Analysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation. GFP+CD4+ and GFP-CD4+ splenocytes were sorted from DEREG and DEREG/Scurfy mice. These cells were activated with anti-CD3/CD28 antibodies, and then transduced with Foxp3-expressing retrovirus (pGCSamIN, NGFR marker). NGFR+ T cells sorted were subjected to microarray analysis (Affymetrix, mouse genome 430 2.0 array). To normalize the experimental conditions, Tregs (GFP+ T cells from DEREG) and Tconv (GFP- T cells from DEREG) were also activated and transduced with empty vector. Two replicates each.

2012-11-05 | E-GEOD-25252 | biostudies-arrayexpress

Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [RNA-seq]

Project description:Regulatory T (Treg) cells are essential for immune homeostasis but inhibit immune rejection of cancer. Strategies to disrupt Treg-mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for this failure are poorly understood. By modeling Treg-targeted immunotherapy in mice, we find that a subset of CD4+ Foxp3- conventional T (Tconv) cells with potent suppressive function undergoes activation and expansion upon depletion of Foxp3+ Treg cells and limits therapeutic efficacy. We noted that Foxp3- Tconv cells within tumors adopt a Treg-like transcriptional profile upon Treg depletion and acquire suppressive function. This is attributable to a Th2-like subset of CD4+ Tconv cells marked by expression of (C-C motif) receptor 8 (CCR8) and enriched in Treg-associated transcripts. CCR8+ Tconv cells are found in mouse and human tumors. Upon Treg depletion, CCR8+ Tconv cells undergo systemic and intratumoral activation and expansion, resulting in IL-10 dependent suppression of anti-tumor immunity. Consequently, conditional deletion of Il10 within T cells augments anti-tumor efficacy upon Treg-depletion in mice, and antibody blockade of IL-10 signaling synergizes with Treg depletion to overcome treatment resistance. These findings reveal a secondary layer of immunosuppression by Tconv cells released upon therapeutic Treg depletion and suggest that broader consideration of suppressive function within the T cell lineage is required for development of effective Treg-targeted therapies.

2024-01-11 | GSE236823 | GEO

Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [scRNA-seq]

2024-01-11 | GSE236824 | GEO