Sphingosine 1-phosphate maintains naïve T cell by regulating apoptotic signaling
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ABSTRACT:
PROVIDER: PRJNA914645 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22840600_1.fastq.gz | Fastqsanger.gz | |||
| SRR22840600_2.fastq.gz | Fastqsanger.gz | |||
| SRR22840601_1.fastq.gz | Fastqsanger.gz | |||
| SRR22840601_2.fastq.gz | Fastqsanger.gz | |||
| SRR22840602_1.fastq.gz | Fastqsanger.gz |
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Project description:Effective immunity requires a large, diverse naïve T cell repertoire circulating among lymphoid organs in search of antigen. Sphingosine 1-phosphate (S1P) and its receptor S1PR1 contribute by both directing T cell migration and supporting T cell survival. Here, we address how S1P enables T cell survival, and the implications for patients treated with S1PR1 antagonists. Contrary to expectations, we found that S1PR1 limits apoptosis by maintaining the appropriate balance of BCL2 family members via restraint of JNK activity. Interestingly, the same residues of S1PR1 that enable receptor internalization are required to prevent JNK overactivation and limit apoptosis. Findings in mice were recapitulated in ulcerative colitis patients treated with the drug ozanimod, and the loss of naïve T cells limited B cell responses. Our findings highlight an unexpected effect of S1PR1 antagonists on the ability to mount immune responses within lymph nodes, beyond their effect on lymph node egress.
2024-02-21 | GSE221482 | GEO
Project description:total RNA from mouse (male c57BL/6) spleen labeled with Cy3 vs total RNA from mouse (male c57BL/6) B cells treated with Sphingosine-1-phosphate labeled with Cy5- time course with repeats Keywords: ordered
2003-04-14 | GSE396 | GEO
Project description:Novel binding proteins for bioactive lipid mediator sphingosine 1-phosphate (S1P) were searched in the plasma from apolipoprotein M/albumin double deficient mice.
2019-09-04 | PXD015023 | Pride
Project description:RNA sequencing was used to evaluate genes regulated in C3H10T1/2 cells by the G protein-coupled receptor agonist sphingosine 1-phosphate.
2021-01-02 | GSE108681 | GEO
Project description:Sphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphoryled by the actions of two S1P-specific phosphatases, sphingosine 1-phosphate phosphatase 1 and 2. To identify the physiologic functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1-/- mice appeared normal at birth but during the first week of life, they exhibited stunted growth, suffered desquamation, and most died before weaning. Interestingly, the epidermal permeability barrier developed normally during embryogenesis. Sgpp1 -/- pups and surviving adults exhibited epidermal hyperplasia and abnormal expression of keratinocyte differentiation markers. Keratinocytes isolated from Sgpp1 -/- skin had increased intracellular S1P levels, and expressed a gene expression profile that indicated enhanced differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis. Comparison of KO vs. WT with five replications per treatment sample
2013-08-09 | E-GEOD-40368 | biostudies-arrayexpress
Project description:Sphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphoryled by the actions of two S1P-specific phosphatases, sphingosine 1-phosphate phosphatase 1 and 2. To identify the physiologic functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1-/- mice appeared normal at birth but during the first week of life, they exhibited stunted growth, suffered desquamation, and most died before weaning. Interestingly, the epidermal permeability barrier developed normally during embryogenesis. Sgpp1 -/- pups and surviving adults exhibited epidermal hyperplasia and abnormal expression of keratinocyte differentiation markers. Keratinocytes isolated from Sgpp1 -/- skin had increased intracellular S1P levels, and expressed a gene expression profile that indicated enhanced differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis.
2013-08-09 | GSE40368 | GEO
Project description:Background: Increased proliferation of airway smooth muscle (ASM) cells leading to hyperplasia and increased ASM mass is one of the most characteristic features of airway remodelling in asthma. A bioactive lipid, sphingosine-1-phosphate (S1P), has been suggested to affect airway remodelling by stimulation of human ASM cell proliferation. Objective: To investigate the effect of S1P on signalling and regulation of gene expression in ASM cells from healthy and asthmatic individuals. Methods: ASM cells grown from bronchial biopsies of healthy and asthmatic individuals were exposed to S1P. Gene expression was analysed using microarray, real-time PCR and western blotting. Receptor signalling and function was determined by mRNA knockdown and intracellular calcium mobilisation experiments. Results: S1P potently regulated the expression of more than 80 genes in human ASM cells, including several genes known to be involved in the regulation of cell proliferation and airway remodelling (HBEGF, TGFB3, TXNIP, PLAUR, SERPINE1, RGS4). S1P acting through S1P2 and S1P3 receptors activated intracellular calcium mobilisation and extracellular signal-regulated and Rho-associated kinases to regulate gene expression. S1P-induced responses were not inhibited by corticosteroids and did not differ significantly between ASM cells from healthy and asthmatic individuals. Conclusion: S1P induces a steroid-resistant, pro-remodelling pathway in ASM cells. Targeting S1P or its receptors could be a novel treatment strategy for inhibiting airway remodelling in asthma. Airway smooth muscle cells from 3 healthy donors were cultured and stimulated for 4 h with sphingosine-1-phosphate (100 nM) or medium control. Total RNA was extracted and analysed using Affymetrix Human Exon 1.0 ST arrays.
2015-06-18 | E-GEOD-58657 | biostudies-arrayexpress
Project description:Abstract Background Sphingosine 1-phosphate (S1P), a lysophospholipid, is involved in various cellular processes such as migration, proliferation, and survival. To date, the impact of S1P on human glioblastoma is not fully understood. Particularly, the concerted role played by matrix metalloproteinases (MMP) and S1P in aggressive tumor behavior and angiogenesis remains to be elucidated. Results To gain new insights in the effect of S1P on angiogenesis and invasion of this type of malignant tumor, we used microarrays to investigate the gene expression in glioblastoma as a response to S1P administration in vitro. We compared the expression profiles for the same cell lines under the influence of epidermal growth factor (EGF), an important growth factor. We found a set of 72 genes that are significantly differentially expressed as a unique response to S1P. Based on the result of mining full-text articles from 20 scientific journals in the field of cancer research published over a period of five years, we inferred gene-gene interaction networks for these 72 differentially expressed genes. Among the generated networks, we identified a particularly interesting one. It describes a cascading event, triggered by S1P, leading to the transactivation of MMP-9 via neuregulin-1 (NRG-1), vascular endothelial growth factor (VEGF), and the urokinase-type plasminogen activator (uPA). This interaction network has the potential to shed new light on our understanding of the role played by MMP-9 in invasive glioblastomas. Conclusions Automated extraction of information from biological literature promises to play an increasingly important role in biological knowledge discovery. This is particularly true for high-throughput approaches, such as microarrays, and for combining and integrating data from different sources. Mining full-text articles, as opposed to abstracts only, may hold the key to unraveling previously unknown relationships between biological entities and could develop into an indispensable instrument in the process of formulating novel and potentially promising hypotheses. Keywords: Sphingosine 1-phosphate treatment, glioblastoma, epidermal growth factor
2006-05-13 | GSE4817 | GEO
Project description:A Pseudomonas aeruginosa-derived neutral ceramidase (PaCDase) isolated from a patient with atopic dermatitis was shown to effectively degrade ceramide in the presence of Staphylococcus aureus-derived lipids or neutral detergents. To understand the effect of ceramide metabolites on the functions of differentiating keratinocytes, we have conducted genes expressions analysis from PaCDase-, sphingosine-1-phosphate (S1P)-treated or untreated three-dimensionally cultured human primary keratinocytes, which form a stratum corneum, in the presence of Triton X-100 using high resolution DNA microarray.
2014-12-25 | GSE53670 | GEO
Project description:Sphingosine 1-phosphate (S1P), a pro-tumor survival bioactive lysophospholipid, generated by sphingosine kinase 1 (SphK1), regulates lymphocyte egress into circulation via transducing S1P receptor 1 (S1PR1) signalling, and also plays a role in the differentiation of regulatory T cells and T helper-17 cells. However, the mechanisms by which receptor-independent SphK1/S1P signallng regulates anti-tumor T cell activity remain unknown. Using melanoma antigen gp100 reactive T cells deficient in Sphk1, we found that Pmel-Sphk1-/- T cells maintained central memory phenotype, showed higher mitochondrial respiration, and exhibited resistance to TGF-β mediated suppression. Mechanistically, we discovered a direct correlation between SphK1 generated intracellular S1P and PPARγ (peroxisome proliferator-activated receptor gamma) activity, which in turn regulate lipolysis in T cells. Genetic, molecular or pharmacologic inhibition of SphK1 or PPARγ improved metabolic fitness and anti-tumor activity of T cells. Further, inhibition of SphK1 and PD1 together led to long-term control of melanoma. Overall, these data highlight the clinical potential of targeting SphK1/S1P for improved anti-cancer adoptive T cell immunotherapy.
2019-07-31 | GSE129489 | GEO