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Single-cell transcriptomics reveal hyperacute cytokine and immune checkpoint axis in patients with poor neurological outcomes after cardiac arrest [BRI]

ABSTRACT: Single-cell transcriptomics reveal hyperacute cytokine and immune checkpoint axis in patients with poor neurological outcomes after cardiac arrest [BRI]

PROVIDER: PRJNA823020 | ENA |

REPOSITORIES: ENA

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Single-cell transcriptomics reveal hyperacute cytokine and immune checkpoint axis in patients with poor neurological outcomes after cardiac arrest [BRI]

Project description:Neurological injury is a major driver for mortality among patients hospitalized after cardiac arrest (CA). The early systemic inflammatory response after CA is associated with neurological injury and mortality but remains poorly defined. We determine the innate immune network induced by clinical CA at single-cell resolution. Immune cell states diverge as early as 6h post-arrest between patients with good or poor neurological outcomes at hospital discharge. Nectin-2+ monocytes and Tim-3+ natural killer (NK) cell subpopulations associate with poor outcomes, and interactome analysis highlight their cross-talk via cytokines and immune checkpoints. Ex vivo studies on peripheral blood cells from CA patients demonstrate that immune checkpoints are a compensatory mechanism for the resolution of inflammation after CA. IFNγ/IL-10 induce Nectin-2 on monocytes; in a negative feedback loop, Nectin-2 suppresses IFNγ production by NK cells. The initial hours after CA may represent a window for therapeutic intervention in the resolution of inflammation via immune checkpoints.

2023-06-01 | GSE200118 | GEO

Single-cell transcriptomics reveal hyperacute cytokine and immune checkpoint axis in patients with poor neurological outcomes after cardiac arrest.

Project description:Single-cell transcriptomics reveal hyperacute cytokine and immune checkpoint axis in patients with poor neurological outcomes after cardiac arrest.

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Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome

2023-06-01 | GSE200117 | GEO

Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome

Project description:Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome

| PRJNA823021 | ENA

Prediction of neurological outcomes shortly after cardiac arrest

Project description:Prediction of neurological outcomes shortly after cardiac arrest would represent a major breakthrough. We tested the ability of gene expression profiles of blood cells to predict outcome in cardiac arrest patients. 35 consecutive cardiac arrest patients treated with therapeutic hypothermia (33Â°C for 24h) were included in this prospective monocentre study. Cerebral Performance Category (CPC) was determined at discharge and 6 months later. All patients had blood sampling at the end of hypothermia. Gene expression profiles of blood cells were determined using 25,000~gene microarray in two groups of patients: good outcome (CPC 1-2) and bad outcome (CPC 3-5).

2013-06-01 | E-GEOD-29540 | biostudies-arrayexpress

Prediction of neurological outcomes shortly after cardiac arrest

2013-06-01 | GSE29540 | GEO

Single-cell transcriptomics reveal hyperacute cytokine and immune checkpoint axis in patients with poor neurological outcomes after cardiac arrest.

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-06-01 | GSE200119 | GEO

Diverse NKT cells regulate early inflammation and neurological outcomes after cardiac arrest and resuscitation

Project description:Neurological injury drives most deaths and morbidity among patients hospitalized for out-of-hospital cardiac arrest (OHCA). Despite its clinical importance, there are no effective pharmacological therapies targeting post-cardiac arrest (CA) neurological injury. Here we analyzed circulating immune cells from a large OHCA patient cohort, finding that lymphopenia independently associated with poor neurological outcomes. Single cell RNA-sequencing of immune cells showed that T cells with features of both innate T cells and natural killer (NK) cells were increased in patients with favorable neurological outcomes. We more specifically identified an early increase in circulating diverse NKT cells (dNKT) in a separate cohort of OHCA patients with good neurological outcomes. These cells harbored a diverse T cell receptor repertoire but were consistently specific for sulfatide antigen. In mice, we found that sulfatide-specific dNKT cells trafficked to the brain after CA and resuscitation. In the brains of mice lacking NKT cells (Cd1d-/-), we observed increased inflammatory chemokine and cytokine expression and accumulation of macrophages when compared with wild-type mice. Cd1d-/- mice also had increased neuronal injury, neurological dysfunction, and worse mortality after CA. To therapeutically enhance dNKT cell activity, we treated mice with sulfatide lipid after CA, showing that it improved neurological function. Together, these data show that sulfatide-specific dNKT cells are associated with good neurological outcomes after clinical OHCA and are neuroprotective in mice after CA. Strategies to enhance the number or function of dNKT cells may thus represent a treatment approach for CA.

2025-01-30 | GSE280524 | GEO