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Characterization of human hepatic natural killer cells in end-stage chronic liver diseases

ABSTRACT: Characterization of human hepatic natural killer cells in end-stage chronic liver diseases

PROVIDER: PRJNA901498 | ENA |

REPOSITORIES: ENA

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Characterization of human hepatic natural killer cells in end-stage chronic liver diseases

Project description:Hepatic Natural Killer (he-NK) cells are innate immune effectors that contribute to immune tolerance and eliminate dangerous “non-self” antigens. He-NK cells fall into two groups, liver resident (rNK) cells, mainly cytokine secretors, and infiltrating conventional NK (cNK) cells, which are cytotoxic. He-NK cell dysfunction and contribution to end-stage liver disease are not fully understood. The present study evaluates the transcriptomes of he-NK subpopulations in chronic hepatic disease of different etiologies, including sterile inflammation (non-alcoholic steatohepatitis - NASH), autoimmunity (primary sclerosing cholangitis - PSC), and viral infection (hepatitis C - HCV).

2023-03-22 | GSE217968 | GEO

Etiology of end-stage liver cirrhosis impacts hepatic natural killer cell heterogenicity.

Project description:The natural killer (NK) cell population is a critical component of the innate immune compartment of the liver, and its functions are deeply affected by the surrounding environment. In the late stage of fibrosis, NK cells become dysfunctional, but the influence of disease etiology on NK cell behavior during cirrhosis remains unclear. Using single-cell RNA sequencing (scRNA-seq), we characterized the hepatic NK cells from end-stage cirrhotic livers from subjects with non-alcoholic steatohepatitis (NASH), chronic hepatitis C infection (HCV) and primary sclerosing cholangitis (PSC). Here, we show that although NK cells shared similar dysfunctions, the disease etiology impacts hepatic NK cell heterogeneity. Therapeutical strategies targeting NK cells for the prevention or treatment of fibrosis should consider liver disease etiology in their design.

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Expression profiling of Natural killer B cells

Project description:Investigation of global gene expression levels between B cells, Natural killer cells and Natural killer B cells Gene expression profiling using sorted B cells, Natural killer cells and Natural killer B cells from WT mouse spleen. Total RNA extracted from WT cells were quantified by the NanoDrop ND-1000 and RNA integrity was assessed by standard denaturing agarose gel electrophoresis. The sample preparation and microarray hybridization were performed based on the NimbleGenâs standard protocols.

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Transcription profiling of neonatal and adult mouse natural killer cells

Project description:Comparing global gene expression of neonatal and adult natural killer cells to determine if differences in gene expression suggest that different developmental pathways during hematopoiesis are followed in the fetal and adult mouse to produce mature natural killer cells.

2005-10-01 | E-MEXP-354 | biostudies-arrayexpress

Expression profiling of Natural killer B cells

Project description:Investigation of global gene expression levels between B cells, Natural killer cells and Natural killer B cells

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Hepatic miR20b promotes nonalcholic fatty liver diseases by targeting PPARα

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Natural Killer Cells from High Grade Serous Ovarian Carcinoma ascites

Project description:Natural killer cells were extracted from the peritoneal cells of ascites of high grade serous ovarian carcinoma patients.

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Extracellular vesicle-mediated communication between hepatocytes and natural killer cells promotes hepatocellular tumorigenesis

Project description:Hepatocellular carcinoma (HCC) is frequently characterized by metabolic and immune remodeling in the tumor microenvironment. We previously discovered that liver-specific deletion of fructose-1, 6-bisphphotase 1 (FBP1), a gluconeogenic enzyme ubiquitously suppressed in HCC tissues, promotes liver tumorigenesis, and induces metabolic and immune perturbations closely resembling human HCC. However, the underlying mechanisms remain incompletely understood. Here we reported that FBP1-deficient livers exhibit diminished amounts of natural killer (NK) cells and accelerated tumorigenesis. Using the diethylnitrosamine-induced HCC mouse model, we analyzed potential changes in the immune cell populations purified from control and FBP1-depleted livers and found that NK cells were strongly suppressed. Mechanistically, FBP1 attenuation in hepatocytes derepresses an EZH2-dependent transcriptional program to inhibit PKLR expression. This leads to reduced levels of PKLR cargo proteins sorted into hepatocyte-derived EVs, dampened activity of EV-targeted NK cells, and accelerated liver tumorigenesis. Our study demonstrated that hepatic FBP1 depletion promotes HCC-associated immune remodeling, partly through the transfer of hepatocyte-secreted, PKLR-attenuated EVs to NK cells.

2023-03-11 | PXD026822 | Pride

Hepatic insulin resistance promotes fructose-enriched diet-induced fatty liver diseases.

Project description:Hepatic insulin resistance promotes fructose-enriched diet-induced fatty liver diseases.

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Natural Killer cells treated with arachidonic acid, IL-2 and ascites

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