Expression data between FOXP3 wild type and 2T>C(mut)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41087 | GEO | 2013/03/08
SECONDARY ACCESSION(S): PRJNA175731
REPOSITORIES: GEO
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Project description:Investigation of the role of FOXP3 in CD4+ T effector cells. FOXP3 is transiently upregulated in T effector cells under activation. This temporary expression in Teff cells is insufficient to suppress expression of reported targets of FOXP3 repressor activity. The role of FOXP3 in T effector cells remains unclear. We used microarray analysis to detail the differentially expressed genes between FOXP3 wild type and 2T>C(mut) clones and identified classes of up-regulated or down-regulated genes based upon FOXP3 expression. We used T effector cells from one IPEX disease carrier mother that consist of a mixed population ofFOXP3 wild type and 2T>C(mut) clones. We activated them using anti-CD3, anti-CD28. We compareFOXP3 wild type and 2T>Cl clones at different stages: resting phase and activated phase at 72hrs.
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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.
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Project description:Expression data between FOXP3 wild type and 2T>C(mut)
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