Plasma kynurenine mediated pathological communication between gut microbiota and ventricular remodeling in children with pressure overload
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE210833 | GEO | 2023/07/19
REPOSITORIES: GEO
Similar Datasets
Project description:Plasma kynurenine mediated pathological communication between gut microbiota and ventricular remodeling in children with pressure overload
| PRJNA867689 | ENA
Project description:We report the gene expression (obtained by next generation RNAseq) of inducible CD103+ dendritic cells, iCD103 cells, stimulated with both murine herpesvirus-68 and the immunomodulatory tryptophan derivative kynurenine (kyn). This study provides data on how tryptophan derivatives can modulate pro-inflammatory cytokine expression in virus treated dendritic cells.
2021-01-01 | GSE160307 | GEO
Project description:Metabolic deregulation and immune escape are pivotal hallmarks of cancer; however, the profile of metabolic reprogramming in oral squamous cell carcinoma (OSCC) and how it drives immune escape remain unclear. We identified significant metabolic disorders in OSCC. Amino acid metabolism, especially tryptophan/kynurenine metabolism, was altered. Here, we found that kynurenine promotes migration, invasion, and proliferation in vitro and in vivo. In addition, most immune checkpoints were upregulated in patients with high kynurenine levels. We then identified that kynurenine can promote Siglec-15 expression via AhR activation. Furthermore, tumor-derived kynurenine can directly exhaust CD8+ T cells, whereas blocking of kynurenine transporters reversed this effect. Moreover, we found that ectopic expression of Siglec-15 can promote immune escape in tumor microenvironment (TME) by suppressing T cell infiltration and inducing CD8+ T cell exhaustion in vivo, while targeting AhR reduces kynurenine-mediated immune escape. Finally, we design NH2-MSNs nanoparticles to deliver Siglec-15 small interfering RNA, which successfully remodels the TME and enhances anti-PD-1 efficacy in tumor-bearing immunocompetent mice. Clinically, Siglec-15 expression is correlated with AhR expression and high infiltration of exhausted CD8+ T cells. These findings reveal that the Kyn/AhR/Siglec-15 signaling pathway is a novel immunometabolism mechanism in OSCC, thus opening a new therapeutic avenue for metabolic immunotherapy.
2024-07-03 | GSE222673 | GEO
Project description:Dysregulation of the kynurenine (Kyn) pathway has been associated with the progression of Huntington's disease (HD). In particular, elevated levels of the kynurenine metabolites 3-hydroxy kynurenine (3-OH-Kyn) and quinolinic acid (Quin), have been reported in the brains of HD patients as well as in rodent models of HD. The production of these metabolites is controlled by the activity of kynurenine mono-oxygenase (KMO), a mitochondrial outer membrane enzyme which catalyzes the synthesis of 3-OH-Kyn from Kyn. Thus inhibiting KMO is expected to produce a beneficial effect in Huntington's Disease (HD) patients, hopefully reversing their phenotype to match healthy subjects. To test this effect, we acutely treated a mouse model of HD (R6/2, a transgenic mouse model of HD which contains a human HTT gene containing 90 CAG repeats) and wild type mice with a KMO inhibitor, and separately used a mock treatment on both the transgenic mice and wild type mice. The goal of this project is to analyze the RNA-seq data and find gene expression changes associated with the KMO inhibitor
2017-10-30 | GSE106161 | GEO
Project description:Dysregulation of the kynurenine (Kyn) pathway has been associated with the progression of Huntington's disease (HD). In particular, elevated levels of the kynurenine metabolites 3-hydroxy kynurenine (3-OH-Kyn) and quinolinic acid (Quin), have been reported in the brains of HD patients as well as in rodent models of HD. The production of these metabolites is controlled by the activity of kynurenine mono-oxygenase (KMO), a mitochondrial outer membrane enzyme which catalyzes the synthesis of 3-OH-Kyn from Kyn. Thus inhibiting KMO is expected to produce a beneficial effect in Huntington's Disease (HD) patients, hopefully reversing their phenotype to match healthy subjects. To test this effect, we chronically treated a mouse model of HD (R6/2, a transgenic mouse model of HD which contains a human HTT gene containing 90 CAG repeats) and wild type mice with a KMO inhibitor for 8 weeks, and separately used a mock treatment on both the transgenic mice and wild type mice. The goal of this project is to analyze the RNA-seq data and find gene expression changes associated with the KMO inhibitor.
2017-10-30 | GSE105158 | GEO
Project description:Nasopharyngeal carcinoma (NPC)-mediated immunosuppression within the tumor microenvironment (TME) frequently culminates in the failure of otherwise promising immunotherapies, underscoring the imperative to develop strategies to counteract the tumor's ability to foster an immunologically "cold" TME. In this study, we identify tumor-intrinsic FLI1 as a critical mediator in impairing T cell anti-tumor immunity through bioinformatic analysis. A mechanistic inquiry reveals that FLI1 orchestrates the expression of CBP and STAT1, facilitating chromatin accessibility and transcriptional activation of IDO1 in response to T cell-released IFN-γ. This regulatory cascade ultimately leads to augmented IDO1 expression, resulting in heightened synthesis of kynurenine (Kyn) in tumor cells. This, in turn, fosters CD8+ T cell exhaustion and regulatory T cell (Treg) differentiation, a process that redounds to the advantage of tumor cell survival.
2024-04-18 | GSE247897 | GEO
Project description:Nasopharyngeal carcinoma (NPC)-mediated immunosuppression within the tumor microenvironment (TME) frequently culminates in the failure of otherwise promising immunotherapies, underscoring the imperative to develop strategies to counteract the tumor's ability to foster an immunologically "cold" TME. In this study, we identify tumor-intrinsic FLI1 as a critical mediator in impairing T cell anti-tumor immunity through bioinformatic analysis. A mechanistic inquiry reveals that FLI1 orchestrates the expression of CBP and STAT1, facilitating chromatin accessibility and transcriptional activation of IDO1 in response to T cell-released IFN-γ. This regulatory cascade ultimately leads to augmented IDO1 expression, resulting in heightened synthesis of kynurenine (Kyn) in tumor cells. This, in turn, fosters CD8+ T cell exhaustion and regulatory T cell (Treg) differentiation, a process that redounds to the advantage of tumor cell survival.
2024-04-18 | GSE247896 | GEO
Project description:Nasopharyngeal carcinoma (NPC)-mediated immunosuppression within the tumor microenvironment (TME) frequently culminates in the failure of otherwise promising immunotherapies, underscoring the imperative to develop strategies to counteract the tumor's ability to foster an immunologically "cold" TME. In this study, we identify tumor-intrinsic FLI1 as a critical mediator in impairing T cell anti-tumor immunity through bioinformatic analysis. A mechanistic inquiry reveals that FLI1 orchestrates the expression of CBP and STAT1, facilitating chromatin accessibility and transcriptional activation of IDO1 in response to T cell-released IFN-γ. This regulatory cascade ultimately leads to augmented IDO1 expression, resulting in heightened synthesis of kynurenine (Kyn) in tumor cells. This, in turn, fosters CD8+ T cell exhaustion and regulatory T cell (Treg) differentiation, a process that redounds to the advantage of tumor cell survival.
2024-04-18 | GSE247895 | GEO
Project description:Right ventricular (RV) dysfunction following left ventricular (LV) failure is associated with poor prognosis. RV remodeling is thought initiated by the increase in the afterload of RV due to secondary pulmonary hypertension (PH) to impaired LV function; however, RV molecular changes might occur in earlier stages of the disease. cGMP (cyclic guanosine monophosphate)-phosphodiesterase 5 (PDE5) inhibitors, widely used to treat PH through their pulmonary vasorelaxation properties, have shown direct cardiac benefits, but their impacts on the RV in LV diseases are not fully determined. Here we show that RV molecular alterations occur early in the absence of RV hemodynamic changes during LV pressure-overload and are ameliorated by PDE5 inhibition. Two-day moderate LV pressure-overload (transverse aortic constriction) neither altered RV pressure/ function nor RV weight in mice, while it induced only mild LV hypertrophy. Importantly, pathological molecular features were already induced in the RV free wall myocardium, including up-regulation of gene markers for hypertrophy and inflammation, and activation of extracellular signal-regulated kinase (ERK) and calcineurin. Concomitant PDE5 inhibition (sildenafil) prevented induction of such pathological genes and activation of ERK and calcineurin in the RV as well as in the LV. Importantly, dexamethasone also prevented these RV molecular changes, similarly to sildenafil treatment. These results suggest the contributory role of inflammation to the early pathological interventricular interaction between RV and LV. The current study provides the first evidence for the novel early molecular cross-talk between RV and LV, preceding RV hemodynamic changes in LV disease, and supports the therapeutic strategy of enhancing cGMP signaling pathway to treat heart diseases.
| S-EPMC5886579 | biostudies-literature
Project description:The ligand-activated transcription factor Aryl Hydrocarbon Receptor (AHR) regulates cellular detoxification, proliferation, and immune evasion in a range of cell types and tissues, including cancer cells. In this study, we used RNA-seq to identify the signature of AHR target genes regulated by the pollutant 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and the endogenous ligand kynurenine (Kyn), a tryptophan-derived metabolite. This approach identified a signature of six genes (CYP1A1, ALDH1A3, ABCG2, ADGFR1, and SCIN) as commonly activated by endogenous or exogenous ligands of AHR in multiple colon cancer cell lines. Among these, the actin-severing protein Scinderin (SCIN) was necessary for cell proliferation; SCIN downregulation limited cell proliferation and its expression increased it. SCIN expression is elevated in a subset of colon cancer patient samples, which also contain elevated β-catenin levels. Remarkably, SCIN expression promotes nuclear translocation of β-catenin and activates the WNT pathway. Our study identified a new mechanism for adhesion-mediated signaling in which SCIN, likely via its ability to alter the actin cytoskeleton, facilitates the nuclear translocation of β-catenin.
2023-06-12 | GSE212795 | GEO