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Engineered Tr1 cells designed for clinical use can eliminate primary pediatric AML blasts

ABSTRACT: Engineered Tr1 cells designed for clinical use can eliminate primary pediatric AML blasts

PROVIDER: PRJNA591564 | ENA |

REPOSITORIES: ENA

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Engineered Tr1 cells designed for clinical use can eliminate primary pediatric AML blasts

Project description:Purpose: To investigate the transcriptome of primary pediatric acute myeloid leukemia to identify molecular signatures correlated with sensitivity to LV-10 mediated killing Method: RNA sequencing of polyA enriched pediatric acute myeloid leukemia bone marrow aspirates Results: pAML killing sensitivity is associated with the expression of a myeloid maturation signature, while resistant pAMLs expressed a more stem cell-like signature Conclusions: Pediatric acute myeloid leukemia samples have different sensitivities to killing by LV-10 in vitro and the transcriptomes of killing-sensitive and killing-resistant lines differ

2020-11-10 | GSE140960 | GEO

The transcriptomic differences between Th1, Tr1, and Tneg cells in controlled human malaria infection

Project description:This study was designed to determine the differences in gene transcripts between CD4+ T helper (Th)1, Tr1, and Tneg cells during controlled human malaria infection.

2019-11-07 | GSE139990 | GEO

The transcriptomic differences between Th1, Tr1, Treg, and Tneg cells in Leishmania donovani-infected mice

Project description:This study was designed to determine the differences in gene transcripts between CD4+ T helper (Th)1, Tr1, Treg, and Tneg cells in L. donovani-infected mice.

2019-11-06 | GSE139933 | 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

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

IL-10-Engineered Human CD4+ Tr1 Cells Eliminate Myeloid Leukemia in an HLA Class I-Dependent Mechanism.

Project description: Not available

| S-EPMC5628869 | biostudies-other

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

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

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

Desulfurella amilsii strain:TR1

Project description:Desulfurella amilsii strain:TR1 Genome sequencing

| PRJNA307095 | ENA