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Comparison of different T cell differentiation states by RNA-seq analysis identifies BX-795 induced Th-IL-2 cells

ABSTRACT: Comparison of different T cell differentiation states by RNA-seq analysis identifies BX-795 induced Th-IL-2 cells

PROVIDER: PRJNA930436 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23306168.fastq.gz	Fastqsanger.gz
	SRR23306169.fastq.gz	Fastqsanger.gz
	SRR23306170.fastq.gz	Fastqsanger.gz
	SRR23306171.fastq.gz	Fastqsanger.gz
	SRR23306172.fastq.gz	Fastqsanger.gz

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Comparison of different T cell differentiation states by RNA-seq analysis identifies BX-795 induced Th-IL-2 cells

Project description:We here report RNA-seq data on CD4+ T cells from double transgenic allergy-mice (Neunkirchner A. et al.) expressing a humanized T cell receptor (TCR) specific for the major mugwort pollen allergen Art v 1 peptide 23-36 in combination with a humanized HLA-DR molecule at time-point zero (FACS sorted naive CD4+ T cells from murine spleen) and after 120 h of stimulation of such FACS sorted naive T cells with bone-marrow derived dendritic cells (BMDCs) from these mice plus recombinant Art v 1 (rArt v 1) protein and either DMSO (T effector), BX-795 (Th-IL-2) or a mix of TGF-b, anti-IL-4 and anti-IFN-g (iTreg). T cells cultured for 120 h were FACS sorted before RNA extraction to exclude BMDCs (purity > 90 %). These data is supposed to characterize the expression phenotype of T cells differentiated in the presence of BX-795 (Th-IL-2) and extract specific features by comparing it to control phenotypes (naive, T effector, iTreg).

2023-03-17 | GSE224271 | GEO

Rhizobium sp. BX strain:BX

Project description:Rhizobium sp. BX strain:BX Genome sequencing

| PRJNA1131931 | ENA

BX-795 inhibits neuroblastoma growth and enhances sensitivity towards chemotherapy.

Project description:High-risk neuroblastoma (NB) represents a major clinical challenge in pediatric oncology due to relapse of metastatic, drug-resistant disease, and treatment-related toxicities. An analysis of 1235 primary NB patient dataset revealed significant increase in AKT1 and AKT2 gene expression with cancer stage progression. Additionally, Both AKT1 and AKT2 expression inversely correlate with poor overall survival of NB patients. AKT1 and AKT2 genes code for AKT that drive a major oncogenic cell signaling pathway known in many cancers, including NB. To inhibit AKT pathway, we repurposed an antiviral inhibitor BX-795 that inhibits PDK1, an upstream activator of AKT. BX-795 potently inhibits NB cell proliferation and colony growth in a dose-dependent manner. BX-795 significantly enhances apoptosis and blocks cell cycle progression at mitosis phase in NB. Additionally, BX-795 potently inhibits tumor formation and growth in a NB spheroid tumor model. We further tested dual therapeutic approaches by combining BX-795 with either doxorubicin or crizotinib and found synergistic and significant inhibition of NB growth, in contrast to either drug alone. Overall, our data demonstrate that BX-795 inhibits AKT pathway to inhibit NB growth, and combining BX-795 with current therapies is an effective and clinically tractable therapeutic approach for NB.

| S-EPMC8626612 | biostudies-literature

Chlamydia trachomatis L2b/795

Project description:Chlamydia trachomatis L2b/795 genome sequencing

| PRJEA71115 | ENA

Zea mays cultivar:RSQ-795

Project description:Zea mays RSQ-795 Transcriptome

| PRJNA493384 | ENA

Clostridium sporogenes strain:DSM 795

Project description:Clostridium sporogenes DSM 795 Genome sequencing

| PRJNA285281 | ENA

The small molecule inhibitor BX-795 uncouples IL-2 production from inhibition of Th2 inflammation and induces CD4<sup>+</sup> T cells resembling iTreg.

Project description:BackgroundTreg cells have been shown to be an important part of immune-homeostasis and IL-2 which is produced upon T cell receptor (TCR)-dependent activation of T lymphocytes has been demonstrated to critically participate in Treg development.ObjectiveTo evaluate small molecule inhibitors (SMI) for the identification of novel IL-2/Treg enhancing compounds.Materials and methodsWe used TCR-dependent and allergen-specific cytokine secretion of human and mouse T cells, next generation messenger ribonucleic acid sequencing (RNA-Seq) and two different models of allergic airway inflammation to examine lead SMI-compounds.ResultsWe show here that the reported 3-phosphoinositide dependent kinase-1 (PDK1) SMI BX-795 increased IL-2 in culture supernatants of Jurkat E6-1 T cells, human peripheral blood mononuclear cells (hPBMC) and allergen-specific mouse T cells upon TCR-dependent and allergen-specific stimulation while concomitantly inhibiting Th2 cytokine secretion. RNA-Seq revealed that the presence of BX-795 during allergen-specific activation of T cells induces a bona fide Treg cell type highly similar to iTreg but lacking Foxp3 expression. When applied in mugwort pollen and house dust mite extract-based models of airway inflammation, BX-795 significantly inhibited Th2 inflammation including expression of Th2 signature transcription factors and cytokines and influx into the lungs of type 2-associated inflammatory cells such as eosinophils.ConclusionsBX-795 potently uncouples IL-2 production from Th2 inflammation and induces Th-IL-2 cells, which highly resemble induced (i)Tregs. Thus, BX-795 may be a useful new compound for the treatment of allergic diseases.

| S-EPMC10117943 | biostudies-literature

Pyricularia oryzae strain:TH 0003 | isolate:TH 0003

Project description:Pyricularia oryzae TH 0003 Transcriptome - TH 0003_Pool

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Thlaspi arvense cultivar:2020-M2-795

Project description:Thlaspi arvense 2020-M2-795 Resequencing

| PRJNA1239376 | ENA

Gyrodon lividus strain:BX

Project description:Gyrodon lividus strain:BX Genome sequencing and assembly

| PRJNA234843 | ENA