MiRNA expreesion file in FOXP3 positive and negative SZ4 cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE64074 | GEO | 2015/11/28
SECONDARY ACCESSION(S): PRJNA270060
REPOSITORIES: GEO
Similar Datasets
Project description:Regulatory T cells have been shown to adopt a catabolic metabolic programme with increased capacity for fatty acid oxidation fuelled oxidative phosphorylation (OXPHOS). The role of Foxp3 in this metabolic shift is poorly understood. Here we show that Foxp3 was sufficient to induce a significant increase in the spare respiratory capacity of the cell, the extra OXPHOS capacity available to a cell to increased demands on energy in response to work. Foxp3-expressing cells were enhanced in their ability to utilise palmitate for respiration and in addition the activity of electron transport complexes I, II and IV were enhanced following Foxp3 expression. ATP was secreted by both T effector and regulatory T cells and was reduced by mitochondrial respiration inhibitors. Thus Foxp3 imparts a selective advantage in ATP generation capacity to the cell and may exploit this as a source of adenosine for functional immunomodulation. In order to explore possible mechanisms for these differences in metabolism we conducted a comparative quantitative proteomics study to compare the contribution of TGFβ and the transcription factor Foxp3 to the Treg proteome. We used quantitative mass spectrometry to examine differences between proteomes of nuclear and cytoplasmic Foxp3-containing T cells and Foxp3 positive iTreg and Foxp3 negative activated CD4 T cells in addition to human peripheral blood natural Treg. Gene set enrichment analysis of our proteomic datasets demonstrated that Foxp3 drives a significant up regulation of several members of the mitochondrial electron transport chain.
2017-02-15 | PXD001789 | Pride
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
Project description:Comparative transcriptome profiles of patient-derived Sezary cells and cultured Sezary cell line (Hut78) mycosis fungoides cell line (Hut 102) and non-Sezary T cell leukemia cell line (Jurkat) relative to benign CD4+ T cells from individuals with no T cell malignancy. There are three goals. The first and primary goal is to establish a list of genes with differential expression between Sezary cells and the benign CD4+ T cell counter part from individuals without Sezary syndrome. A secondary goal is to examine if these differentially expresses genes in clinical samples of Sezary cells are preserved in Hut78 and Hut102 cells, which are the two most frequently used experimental cell models of Sezary cells in the research community. The third goal is to examine if these Sezary cell specific genes are also present in a non-Sezary T cell malignancy, such as Jurkat cells, which is derived from a non-Sezary cell T cell leukemia patient. Two color experiment, 6 biological replicates (6 unique patients) with Sezary syndrome, 1 Hut78 cell,1 Hut102 cell and 1 Jurkat cell lines as the experimental samples, each compared with a distinct individual with no T cell malignancy of the skin or the blood.
2010-12-31 | E-GEOD-23113 | biostudies-arrayexpress
Project description:Comparative transcriptome profiles of patient-derived Sezary cells and cultured Sezary cell line (Hut78) mycosis fungoides cell line (Hut 102) and non-Sezary T cell leukemia cell line (Jurkat) relative to benign CD4+ T cells from individuals with no T cell malignancy. There are three goals. The first and primary goal is to establish a list of genes with differential expression between Sezary cells and the benign CD4+ T cell counter part from individuals without Sezary syndrome. A secondary goal is to examine if these differentially expresses genes in clinical samples of Sezary cells are preserved in Hut78 and Hut102 cells, which are the two most frequently used experimental cell models of Sezary cells in the research community. The third goal is to examine if these Sezary cell specific genes are also present in a non-Sezary T cell malignancy, such as Jurkat cells, which is derived from a non-Sezary cell T cell leukemia patient.
2010-12-31 | GSE23113 | GEO
Project description:Regulatory T cells (Tregs) are responsible for limiting autoimmunity and chronic inflammation. Foxp3 is a transcription factor that acts as a master regulator of Treg development and function. A serendipitous observation led to the realization that a well-characterized Foxp3gfp reporter mouse, which expresses an N-terminal GFP-Foxp3 fusion protein, is a hypomorph that causes profoundly accelerated autoimmune diabetes on a NOD background. Although natural Treg development and in vitro function is not significantly altered in Foxp3gfp NOD and C57BL/6 mice, Treg fitness function in inflammatory environments is perturbed and TGF?-induced Treg development reduced. Foxp3gfpis unable to interact with the histone acetyltransferase Tip60, the histone deacetylase HDAC7, and the Ikaros family zinc finger 4, Eos, which leads to reduced Foxp3 acetylation and enhanced K48-linked polyubiquitylation. Collectively this leads to an altered transcriptional landscape and reduced Foxp3-mediated gene repression, notably at the hallmark IL-2 promoter. Loss of controlled Foxp3-driven epigenetic modification leads to Treg insufficiency that causes autoimmunity in prone environments. 16 samples overall split between 2 genotypes (wild type and Foxp3 knock in) and two cell types (Tregs and Tconv)
2012-12-07 | E-GEOD-35164 | biostudies-arrayexpress
Project description:Regulatory T cells (Treg) have been shown to adopt a catabolic metabolic programme with increased capacity for fatty acid oxidation fuelled oxidative phosphorylation (OXPHOS). The role of Foxp3 in this metabolic shift is poorly understood. Here we show that Foxp3 was sufficient to induce a significant increase in the spare respiratory capacity of the cell, the extra OXPHOS capacity available to a cell to meet increased demands on energy in response to work. Foxp3-expressing cells were enhanced in their ability to utilise palmitate for respiration and, in addition, the activity of electron transport complexes I, II and IV were enhanced following Foxp3 expression. Foxp3 also imparts a selective advantage in ATP generation capacity, one that might be exploited as a source of adenosine for functional immunomodulation. In order to explore possible mechanisms for these differences in metabolism we conducted a quantitative proteomics study to compare the contribution of TGFβ and the transcription factor Foxp3 to the Treg proteome. We used quantitative mass spectrometry to examine differences between proteomes of nuclear and cytoplasmic Foxp3-containing CD4+ T cells from various sources with Foxp3- activated CD4 T cells, as well as Treg from human peripheral blood. Gene set enrichment analysis of our proteomic datasets demonstrated that Foxp3 expression is associated with a significant up regulation of several members of the mitochondrial electron transport chain. Not only does Foxp3 influence genes directly concerned with immune function, but also with the energy generating functions of Treg.
2017-02-15 | PXD001906 | Pride
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.
2012-11-05 | GSE25252 | GEO
Project description:Using 5 differents approaches, including RNA sequencing, we demonstrated that macrophages that specifically infiltrate renal tumors, express the immunosuppressive transcription factor Foxp3. Examination of the Foxp3 mRNA expression in 3 different cell subsets (including CD4 T cells (CD4), type-1 macrophages (M1) and type-2 macrophages (M2))
2014-05-31 | E-GEOD-56904 | biostudies-arrayexpress
Project description:Naturally occurring CD25+CD4+ regulatory T cells (T reg cells) are currently intensively characterized because of their major importance in modulating host responses to tumors and infections, in preventing transplant rejection, and in inhibiting the development of autoimmunity and allergy. Originally, CD4+ T reg cells were identified exclusively by the constitutive expression of CD25, and many in vivo experiments have been performed using depleting antibodies directed against CD25. However, both the existence of CD25– T reg cells, especially within peripheral tissues, as well as the expression of CD25 on activated conventional T cells, which precludes discrimination between T reg cells and activated conventional T cells, limits the interpretation of data obtained by the use of anti-CD25 depleting antibodies. The most specific T reg cell marker currently known is the forkhead box transcription factor Foxp3, which has been shown to be expressed specifically in mouse CD4+ T reg cells and acts as a master switch in the regulation of their development and function. To address the question of the in vivo role of T reg cells in immunopathology, we have generated bacterial artificial chromosome (BAC)–transgenic mice termed depletion of regulatory T cell (DEREG) mice, which express a diphtheria toxin receptor (DTR) enhanced GFP (eGFP) fusion protein under the control of the foxp3 locus, allowing both detection and inducible depletion of Foxp3+ T reg cells. The gene expression profile of both CD4+eGFP+FoxP3+ and CD4+eGFPnegFoxP3neg cells isolated from DEREG mice was here analyzed by micro array. Keywords: DEREG, FoxP3, FoxP3-EGFP, mouse, regulatory T cell, CD4 CD4+GFP+FoxP3+ and CD4+GFPnegFoxP3neg cells were isolated from DEREG mice by negative selection of CD4+ T cells (Invitrogen Kit) and subsequent FACS sorting for GFP+ and GFPneg cells. Purity was greater than 99 %. cRNA was prepared according to the Affymetrix Labeling Protocol, fragmented and hybridized to Affymetrix GeneChip Mouse Genome 430.
2009-10-03 | E-GEOD-18387 | biostudies-arrayexpress
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