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PDK1 is required for maintenance of CD4+ FoxP3+ regulatory T cell function [Hemizygous]

ABSTRACT: PDK1 is required for maintenance of CD4+ FoxP3+ regulatory T cell function [Hemizygous]

PROVIDER: PRJNA687026 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13282604.fastq.gz	Fastqsanger.gz
	SRR13282605.fastq.gz	Fastqsanger.gz
	SRR13282606.fastq.gz	Fastqsanger.gz
	SRR13282607.fastq.gz	Fastqsanger.gz

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PDK1 is required for maintenance of CD4+ FoxP3+ regulatory T cell function [Hemizygous]

Project description:The goal of this study was to determine the effect of Treg-specific Pdpk1 (PDK1) deletion on the transcriptome of Treg cells. CD4+ YFP+ Treg cells from spleens and peripheral lymph nodes of hemizygous Foxp3 YFP-Cre/0 Pdpk1 +/+ (WT) and Foxp3 YFP-Cre/0 Pdpk1 FL/FL (KO) were sorted, RNA was isolated and RNA-seq libraries were constructed and sequenced by Hiseq2000. Note companion data set using Pdpk1-deleted Treg from Cre-heterozygous mice, which do not develop spontaneous inflammation.

2021-02-11 | GSE163662 | GEO

PDK1 is required for maintenance of CD4+ FoxP3+ regulatory T cell function [heterozygous]

Project description:The goal of this study was to determine the effect of Treg-specific Pdpk1 (PDK1) deletion on the transcriptome of Treg cells in the absence of inflammatory conditions. CD4+ YFP+ Treg cells from spleens and peripheral lymph nodes of Cre-heterozygous Foxp3 YFP-Cre/+ Pdpk1 +/+ (WT) and Foxp3 YFP-Cre/+ Pdpk1 FL/FL (KO) were sorted, RNA was isolated and RNA-seq libraries were constructed and sequenced by Hiseq2500. Note companion data set using hemizygous Cre (induces spontaneous inflammation).

2021-02-11 | GSE163659 | GEO

PDK1 is required for maintenance of CD4+ FoxP3+ regulatory T cell function

Project description:PDK1 is required for maintenance of CD4+ FoxP3+ regulatory T cell function

| PRJNA687017 | ENA

PDK1 is required for maintenance of CD4+ FoxP3+ regulatory T cell function [heterozygous]

Project description:PDK1 is required for maintenance of CD4+ FoxP3+ regulatory T cell function [heterozygous]

| PRJNA687022 | ENA

PDK1 is required for maintenance of CD4+ FoxP3+ regulatory T cell function

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-02-11 | GSE163663 | GEO

Transcription profiling of mouse CD4+ T cells expressing Foxp3 FACS isolated from hemizygouse males to investigate development of regulatory t cell precursors in the absence of a functional foxp3 protein

Project description:To analyze gene expression in in regulatory T cell precursors that develop in the absence of a functional Foxp3 protein as compared to that of normal regulatory T cells Experiment Overall Design: Murine wild-type and mutant (delta) Foxp3 alleles were tagged with EGFP reporters. CD4 positive T cells expressing the respective tagged Foxp3 allele (Foxp3/EGFP and delta Foxp3/EGFP) were isolated from hemizygous male mice by cell sorting using FACS. CD4 positive cells that did not express the EGFP tag were a isolated. Total RNA was prepared and used in the array studies.

2008-06-15 | E-GEOD-6875 | biostudies-arrayexpress

Nemo-like kinase drives Foxp3 stability and is critical for maintenance of immune tolerance by regulatory T cells

Project description:The Foxp3 transcription factor is a crucial determinant of both regulatory T (TREG) cell development and their functional maintenance. Appropriate modulation of tolerogenic immune responses therefore requires tight regulation of Foxp3 transcriptional output, and this involves both transcriptional and post-translational regulation. Here, we show that during T cell activation, phosphorylation of Foxp3 in TREG cells can be regulated by a TGFβ Activated Kinase 1 (TAK1)-Nemo Like Kinase (NLK) signaling pathway. NLK interacts with Foxp3 in TREG cells and directly phosphorylates Foxp3 on multiple serine residues. This phosphorylation results in stabilization of Foxp3 protein levels by preventing association with the STUB1 E3-ubiquitin protein ligase, resulting in both reduced ubiquitination and proteasome-mediated degradation. Conditional TREG cell NLK-knockout (NLKTREG) results in decreased TREG cell-mediated immunosuppression in vivo and NLK-deficient TREG cell animals develop more severe experimental autoimmune encephalomyelitis. Our data suggest a molecular mechanism, in which stimulation of TCR-mediated signaling can induce a TAK1-NLK pathway to sustain Foxp3 transcriptional activity through stabilization of protein levels, thereby maintaining TREG cell suppressive function. Pharmacological manipulation of this phosphorylation-ubiquitination axis may provide therapeutic opportunities for regulating TREG cell function, for example during cancer immunotherapy.

2019-09-02 | PXD011164 | Pride

Hydrogen Deuterium Exchange of PDK1

Project description:This project consisted of three HDX-MS experiments. First, we compared the dimeric PDK1(SKD-PIF) to monomeric PDK1(SKD) and mapped the differences in deuterium incorporation onto the dimer model. We then compared the deuterium incorporation kinetics for the kinase (PDK1(SKD)) and PH (PDK1(PH) domains of PDK1 with full-length PDK1 (PDK1(FL)) in pairwise experiments.

2022-05-20 | PXD027401 | Pride

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

Expression data from MMTV-PDK1 transgenic mice

Project description:The role of PDK1 on mammary tumorigenesis and its interaction with PPARdelta, was assessed. Transgenic mice were generated in which PDK1 was expressed in the mammary epithelium. We used microarrays to analyse global gene expression changes in MMTV-PDK1 transgenic mice versus wild-type mice and determine any differential responses to GW501516 treatment.

2011-02-05 | GSE27083 | GEO

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