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Alterations in gene expression following knockdown of thioredoxin 1 (TR1) with stable viral transduction

ABSTRACT: This experiment was to determine if we could observe changes in gene expression following the attenuation of one of the primary redox regulators of cells - thioredoxin reductase 1. The experiment was set up with two cell lines that expressed different basal levels of TR1. LOX cells represent an aggressive melanoma in xenograft models and are high expressors of TR1 while SK Mel-28 cells represent a non-aggressive melanoma in xenografts adn are low expressors of TR1.

ORGANISM(S): Homo sapiens

PROVIDER: GSE56519 | GEO | 2015/04/28

SECONDARY ACCESSION(S): PRJNA243619

REPOSITORIES: GEO

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Alterations in gene expression following knockdown of thioredoxin 1 (TR1) with stable viral transduction

Project description:This experiment was to determine if we could observe changes in gene expression following the attenuation of one of the primary redox regulators of cells - thioredoxin reductase 1. The experiment was set up with two cell lines that expressed different basal levels of TR1. LOX cells represent an aggressive melanoma in xenograft models and are high expressors of TR1 while SK Mel-28 cells represent a non-aggressive melanoma in xenografts adn are low expressors of TR1. The experimental design was to set up direct comparisons for melanoma cells with the induction of a control miRNA or the miRNA directed against TR1 - with an evaluation of the uninduced situation. Melanoma cell lines stabily transfected with tetracyclin-inducible microRNA - directed at either control, or to TR1.

2015-04-28 | E-GEOD-56519 | biostudies-arrayexpress

Sep15 and TR1 pathways in colon cancer promotion

Project description:Selenoproteins mediate the cancer-preventive properties of the essential nutrient selenium, but also have cancer-promoting effects. We examined the contributions of the 15-kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and cancer metastasis of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially the interferon-gamma-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient cells. In contrast, the Wnt/Beta-catenin pathway was up-regulated in cells that lacked both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, and controversial results of recent human clinical trials involving dietary selenium, our results are important to general public health.

2016-02-01 | GSE55488 | GEO

Gene expression of type 1 regulatory T (Tr1) cells

Project description:Purpose: To identify gene expression patterns in ex vivo isolated human Tr1 cells. Method: RNA sequencing of total mRNA. Results: Differential gene expression of Tr1 and non-Tr1 CD4+ T memory cells. Conclusions: ex vivo type 1 regulatory T cells have a distinct gene expression profile compared to non-Tr1 CD4+ T cell memory cells.

2021-07-02 | GSE169761 | GEO

IL-10 Receptor Signaling is essental for Tr1 cell function in vivo

Project description:Interleukin-10 (IL-10) is essential to maintain intestinal homeostasis. CD4+ T regulatory type 1 (TR1) cells produce large amounts of this cytokine and being therefore currently examined in clinical trials as T-cell therapy in patients with inflammatory bowel disease (IBD). However, factors and molecular signals sustaining TR1 cell regulatory activity still need to be identified in order to optimize the efficiency and to ensure the safety of these trials. We investigated the role of IL-10 signaling in mature TR1 cells in vivo. Double IL-10eGFP Foxp3mRFP reporter mice and transgenic mice with impairment in IL-10 receptor signaling were used to test the activity of TR1 cells in a murine IBD model, a model that resembles the trials performed in humans. The molecular signaling was elucidated in vitro. Finally, we used human TR1 cells, currently employed for cell therapy, to confirm our results. We found that murine TR1 cells expressed functional IL-10 receptor α. TR1 cells with impaired IL-10 receptor signaling lost their regulatory activity in vivo. TR1 cells required IL-10 receptor signaling in order to activate p38 MAP kinase, thereby sustaining IL-10 production, which ultimately mediated their suppressive activity. Finally, we confirmed these data using human TR1 cells. In conclusion TR1 cell regulatory activity is dependent on IL-10 receptor signaling. These data suggest that in order to optimize TR1 cell-based therapy, IL-10 receptor expression has to be taken into consideration.

2016-12-30 | GSE89080 | GEO

Desulfurella amilsii strain:TR1

Project description:Desulfurella amilsii strain:TR1 Genome sequencing

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Expression data for wildtype CD4+ T cells cells differentiated in Tr1 conditions for 2 hours

Project description:Type 1 regulatory T (Tr1) cells are induced by the interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. Here, we show that the transcription factors IRF1 and BATF are induced early during treatment with IL-27 and are required for the differentiation and function of Tr1 cells in vitro and in vivo . Epigenetic and transcriptional analyses reveal that both transcription factors influence chromatin accessibility and expression of genes required for Tr1 cell function. IRF1 and BATF deficiencies uniquely alter the chromatin landscape, suggesting that these factors serve a pioneering function during Tr1 cell differentiation.

2017-01-27 | GSE92940 | GEO

RNA-seq analysis of human antigen-specific type 1 regulatory T cells (Tr1)

Project description:Co-culture of human CD4+ T cells with allogeneeic tolerogenic dendritic cells (DC-10) results in a cell product, called T-allo10, enriched with alloantigen-specific type 1 regulatory T cells (Tr1 cells). CD49b+LAG3+ Tr1 cells and CD49b-LAG3- non-Tr1 cells (DN) were sorted from total T-allo10 cells, and their transcriptomes compared to parental CD4+ T cells, as well as to and control CD49b-LAG3- effector T cells (Teff) sorted from T-allo cells, which were made equivalently to T-allo10 except with using mature dendirtic cells instead of DC-10.

2021-10-27 | GSE160194 | GEO

Pinus jeffreyi cultivar:JP 4801 UBC TR1

Project description:Pinus jeffreyi JP 4801 UBC TR1 Transcriptome - TR1-Y1-B

| PRJNA585319 | ENA

Pinus jeffreyi cultivar:JP 4801 UBC TR1

Project description:Pinus jeffreyi JP 4801 UBC TR1 Transcriptome - TR1-Y5-X

| PRJNA585320 | ENA

RNA-Seq analysis of human Tr1, Tregs and IL10neg cells

Project description:To determine the differentially expressed genes between these subsets and identify the core human in vivo differentiated Tr1 cell gene signature

2019-09-10 | GSE125504 | GEO

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