Homo sapiens
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PROVIDER: PRJNA116683 | ENA |
REPOSITORIES: ENA
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Project description:Regulatory T cells expressing the transcription factor Foxp3 play indispensable roles for the induction and maintenance of immunological self-tolerance and immune homeostasis. Genome-wide mRNA expression-studies have defined canonical signatures of T-cell subsets. Changes in steady-state mRNA levels do, however, often not reflect those of corresponding proteins due to post-transcriptional mechanisms including mRNA translation. Here, we unveil a unique translational signature, contrasting CD4+Foxp3+ regulatory T (TFoxp3+) and CD4+Foxp3- non-regulatory T (TFoxp3-) cells, which imprints subset-specific protein expression. We further show that translation of eukaryotic translation initiation factor 4E (eIF4E) is induced during T-cell activation and, in turn, regulates translation of cell cycle related mRNAs and proliferation in both TFoxp3- and TFoxp3+ cells. Unexpectedly, eIF4E also affects Foxp3 expression and thereby lineage identity. Thus, mRNA-specific translational control directs both common and distinct cellular processes in CD4+ T-cell subset. CD4+/Foxp3+ and CD4+Foxp3- cells were studied ex vivo or activated in vitro for 36h. Both polysome-associated and cytoplasmic RNA was isolated to enables studies of translational control
2013-06-01 | E-GEOD-45401 | biostudies-arrayexpress
Project description:Understanding human regulatory T cells (Tregs) heterogeneity may identify markers of disease pathogenesis and facilitate the development of optimized cellular therapeutics. To better elucidate human Treg subsets, we conducted direct transcriptional profiling of CD4+FOXP3+Helios+ thymic-derived Treg (tTreg) and CD4+FOXP3+Helios- peripherally-induced Treg (pTreg), followed by comparison to CD4+FOXP3-Helios- T conventional (Tconv) cells. This analysis revealed that the coinhibitory receptor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) was highly expressed on tTreg. In this study CD4 T cells were stained for the Treg-associated transcription factors FOXP3 and Helios, and subsequently FACS sorted to yield three populations: tTreg (CD4+FOXP3+Helios+), pTreg (CD4+FOXP3+Helios–) and the reference population Tconv (CD4+FOXP3–Helios–). A direct transcriptional profile was obtained from the recovered RNA from the populations defined as tTreg, pTreg, and Tconv.
2015-04-30 | E-GEOD-61834 | biostudies-arrayexpress
Project description:Type 1 regulatory T (Tr1) cells are one of the regulatory T cell subsets that are characterized by the production of high amount of IL-10 and lack of FOXP3 expression. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue molecule and we have previously reported that LAG3 is expressed on IL-10 producing regulatory T cells. However, naturally occurring Tr1 cells in human secondary lymphoid tissue have not been detected. We identified CD4+CD25-LAG3+ T cells in human tonsil. We compared mRNA expression of five CD4+ T cell subsets in tonsil using microarray analysis (CD4+CD25-LAG3+ T cells, CD4+CD25-CXCR5+PD-1+ follicular helper T cells (TFH), CD4+CD25+ T cells, CD4+CD25-LAG3-CD45RO+ cells and CD4+CD25-LAG3-CD45RO- cells). A human tonsil was obtained from a patient undergoing routine tonsillectomy, and five tonsillar CD4+ T cell subsets were sorted (each 1 x 10^5 cells). There is no biological replication.
2016-04-01 | E-GEOD-73927 | biostudies-arrayexpress
Project description:Type 1 regulatory T (Tr1) cells are one of the regulatory T cell subsets that are characterized by the production of high amount of IL-10 and lack of FOXP3 expression. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue molecule and we have previously reported that LAG3 is expressed on IL-10 producing regulatory T cells. However, naturally occurring Tr1 cells in human secondary lymphoid tissue have not been detected. We identified CD4+CD25-LAG3+ T cells in human tonsil. We compared mRNA expression of five CD4+ T cell subsets in tonsil using microarray analysis (CD4+CD25-LAG3+ T cells, CD4+CD25-CXCR5+PD-1+ follicular helper T cells (TFH), CD4+CD25+ T cells, CD4+CD25-LAG3-CD45RO+ cells and CD4+CD25-LAG3-CD45RO- cells).
2016-04-01 | GSE73927 | GEO
Project description:Understanding human regulatory T cells (Tregs) heterogeneity may identify markers of disease pathogenesis and facilitate the development of optimized cellular therapeutics. To better elucidate human Treg subsets, we conducted direct transcriptional profiling of CD4+FOXP3+Helios+ thymic-derived Treg (tTreg) and CD4+FOXP3+Helios- peripherally-induced Treg (pTreg), followed by comparison to CD4+FOXP3-Helios- T conventional (Tconv) cells. This analysis revealed that the coinhibitory receptor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) was highly expressed on tTreg.
2015-04-30 | GSE61834 | GEO
Project description:Microarray expression analysis depicting MHCII-dependent features of FOXP3-expressing CD4 T regulatory cells
| PRJNA939149 | ENA
Project description:Pioglitazone treatment of CD4+FoxP3- T cells transduced with Pparg and Foxp3 up-regulated a set of genes whose products have been implicated in lipid metabolism pathways. To verify the specificity of this treatment, we performed microarray analysis on Foxp3+Pparg1-transduced CD4+FoxP3- T cells after treatment with other PPARg agonists such as Rosiglitazone (TZD) and GW1929 (non-TZD).
2012-05-04 | GSE37534 | GEO
Project description:Gene expression profiles of subsets of CD4+ T cells according to their expression of FoxP3 and CD45RA were compared. Abstract: FoxP3 is a key transcription factor for the development and function of natural CD4+ regulatory T cells (Tregs). Here we show that human FoxP3+CD4+ T cells are composed of three phenotypically and functionally distinct subpopulations: CD45RA+FoxP3low resting Tregs (rTregs) and CD45RA-FoxP3high activated Tregs (aTregs), both of which are suppressive in vitro, and cytokine-secreting CD45RA-FoxP3low non-suppressive T cells. The proportion of the three subpopulations characteristically altered in cord blood, aged individuals, and patients with immunological diseases. Terminally differentiated aTregs rapidly die while rTregs proliferate and convert into aTregs in vitro and in vivo as shown by the transfer of rTregs into NOD-scid-common gamma-chain-knockout mice and by TCR sequence-based T cell clonotype tracing in peripheral blood of normal individuals. Taken together, the dissection of FoxP3+ cells into subsets enables one to analyze Treg differentiation dynamics and interactions in normal and disease states, and to control immune responses through manipulating particular FoxP3+ subpopulations. RNA was extracted from freshly obtained peripheral blood lymphocytes from a healthy donor that were separated according to their expression of CD25, CD127 and CD45RA after surface staining.
2009-05-21 | E-GEOD-15659 | 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:Regulatory T cells expressing the transcription factor Foxp3 play indispensable roles for the induction and maintenance of immunological self-tolerance and immune homeostasis. Genome-wide mRNA expression-studies have defined canonical signatures of T-cell subsets. Changes in steady-state mRNA levels do, however, often not reflect those of corresponding proteins due to post-transcriptional mechanisms including mRNA translation. Here, we unveil a unique translational signature, contrasting CD4+Foxp3+ regulatory T (TFoxp3+) and CD4+Foxp3- non-regulatory T (TFoxp3-) cells, which imprints subset-specific protein expression. We further show that translation of eukaryotic translation initiation factor 4E (eIF4E) is induced during T-cell activation and, in turn, regulates translation of cell cycle related mRNAs and proliferation in both TFoxp3- and TFoxp3+ cells. Unexpectedly, eIF4E also affects Foxp3 expression and thereby lineage identity. Thus, mRNA-specific translational control directs both common and distinct cellular processes in CD4+ T-cell subset.
2013-06-01 | GSE45401 | GEO