Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human activated T lymphocytes to determine the effects of TX527, a hypocalcemic vitamin D analog

ABSTRACT: Hypocalcemic vitamin D analogs are appealing molecules to exploit the immunomodulatory actions of active vitamin D in vivo. The functional modulation of dendritic cells is regarded as the key mechanism underlying their ability to regulate T cell responses. In contrast, the direct actions of vitamin D and structural analogs on T lymphocytes remain less well characterized. Microarray analysis was performed to gain insight into the direct immunomodulatory actions of TX527, a hypocalcemic vitamin D analog, on human T lymphocytes. Gene expression analysis revealed that TX527 regulated a wide variety of genes involved in different aspects of T cell function, including cellular growth and proliferation, cell death, cellular development, cellular movement and cell-to-cell signalling and interaction. Human CD3+ T cells, isolated from peripheral blood from healthy donors, were activated by anti-CD3/anti-CD28 and cultured in the presence of TX527 (10-8M) or vehicle (ethanol) for 10 days. Expression profiles of TX527-treated and vehicle-treated T cells were compared using Affymetrix Human Genome U133 Plus 2.0 Arrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Femke Baeke

PROVIDER: E-GEOD-23984 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The vitamin D analog, TX527, promotes a human CD4+CD25highCD127low regulatory T cell profile and induces a migratory signature specific for homing to sites of inflammation.

Baeke Femke F Korf Hannelie H Overbergh Lut L Verstuyf Annemieke A Thorrez Lieven L Van Lommel Leentje L Waer Mark M Schuit Frans F Gysemans Conny C Mathieu Chantal C

Journal of immunology (Baltimore, Md. : 1950) 20101203 1

The use of hypocalcemic vitamin D analogs is an appealing strategy to exploit the immunomodulatory actions of active vitamin D in vivo while circumventing its calcemic side effects. The functional modulation of dendritic cells by these molecules is regarded as the key mechanism underlying their ability to regulate T cell reactivity. In this article, we demonstrate the capacity of the vitamin D analog, TX527, to target T cells directly. Microarray analysis of purified human CD3(+) T cells, cultur ...[more]

PMID: 21131424

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Project description:A recently identified unconventional T cell population known as mucosal-associated invariant T (MAIT) cells are characterized by the expression of semi-invariant T cell receptor (TCR) with a canonical TRAV1-2/TRAJ33 (Vα7.2/Jα33). These evolutionary conserved, innate-like T cells recognize vitamin B metabolites, derived from some bacteria and fungi. Due to their presence not only in the T cell repertoire of mucosal surfaces but also in peripheral blood and liver, and their significant involvement in a wide range of diseases, in-depth characterization of human MAIT cells is a timely requirement. Studies that examined the transcriptome, immunoproteome, and whole-cell proteome characterized the role of cytotoxic molecules and cytokines in effector functions of MAIT cells and their relationship with some other immune cell subsets. As MAIT cells are classified under the CD3+ T cell compartment and the majority express surface receptor CD8, identifying their proteomic relationship with CD3+ and CD8+ T cells is pivotal. Thus, a high-resolution dataset was generated using the cell populations sorted from peripheral blood mononuclear cells of three healthy volunteers to describe the whole cell proteomes of MAIT, CD3+, and CD8+ T cells. Trypsin-digested peptide samples obtained from the methanol co-precipitation method were analyzed using an Orbitrap FusionTM TribridTM mass spectrometer (Thermo Fisher Scientific, USA) inline coupled to nanoACQUITY ultra-performance liquid chromatography system (Waters, USA) to acquire data-dependent shotgun proteomic data (DDA-MS) for label-free quantification. Analysis of raw DDA-MS data using MaxQuant software and maxLFQ identified and quantified 4,442 protein groups at a 1% false discovery rate. Further analysis identified 3,680 proteins which were detected with a single UniProt accession and a minimum of 2 unique or razor peptides. Thus this proteomic dataset can be used as a reference proteome for future studies on human MAIT cells.

Dataset Information

Transcription profiling of human activated T lymphocytes to determine the effects of TX527, a hypocalcemic vitamin D analog

Publications

The vitamin D analog, TX527, promotes a human CD4+CD25highCD127low regulatory T cell profile and induces a migratory signature specific for homing to sites of inflammation.

Similar Datasets

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