Project description:Natural Killer (NK) cells play a central role in cell-mediated immune response to cancer. In previous studies number and function of NK-cells have been shown to be positively correlated with HCC outcome. In this study, we have performed a genetic expression analysis comparing mRNA expression by NK cells from HCC patients to patients with the pre-neoplastic condition of liver cirrhosis and to healthy donors. The bioinformatic analysis has been completed by an immunophenotypic study and functional analysis of the main NK cell functions. It is known that NK cells may present functional defects in HCC patients however previous studies have not systematically address the molecular mechanisms associated with these defects by an unbiased genetic expression study. We could identify altered cellular pathways and hypothesize possible mechanisms that could be targeted for restoring an immune-protective NK cell response. NK cells were isolated and sorted from Hepatitis C virus (HCV)-related liver cirrhosis (10 patients), early stage HCC and HCV-related liver cirrhosis (14 patients) and seven healthy donors. RNA from sorted NK cells was processed, labeled and hybridized to Agilent microarrays.
Project description:Natural Killer (NK) cells play a central role in cell-mediated immune response to cancer. In previous studies number and function of NK-cells have been shown to be positively correlated with HCC outcome. In this study, we have performed a genetic expression analysis comparing mRNA expression by NK cells from tumor samples derived from HCC patients to NK cells infiltrating the liver counterpart and to NK cells in the normal liver as controls. The bioinformatic analysis has been completed by an immunophenotypic study, functional analysis and metabolic assessment of the infiltrating NK cells. It is known that NK cells may present functional defects in HCC patients however previous studies have not systematically address the molecular mechanisms associated with these defects by an unbiased genetic expression study. We have identified altered cellular pathways and hypothesized possible mechanisms that could be targeted for restoring an immune-protective NK cell response.
Project description:Liver is a unique immunological organ containing large number of NK cells which play an important role in the maintenance of liver homeostasis, especially the specific liver resident DX5- NK cell subset. We used microarrays to detail the differences of normal DX5- NK cells and the DX5- NK cells in inflammatory environment.
Project description:We report the gene expression profiles of liver sinusoidal Vγ9+Vδ2+ T cells from healthy donors and patients with hepatitis B virus-related chronic liver disease.
Project description:Liver-resident NK (lrNK) cells have been studied in human as well as in mice. In the current study, we compared the transcriptome of three porcine NK cell populations: CD8αhigh cNK cells from peripheral blood, CD8αhigh NK cells isolated from the liver and the liver-specific CD8αdim NK cells using RNA-seq, to gain new insights in the biology of these cells. Overall, our data indicate that lrNK cells show an immature and anti-inflammatory phenotype. We also observed that the CD8αhigh NK cell population present in the liver appears to represent a population with an intermediate phenotype. While the transcriptome of these cells largely overlaps with that of cNK cells, they also express transcripts associated with liver residency, such as CXCR6.
Project description:Somatic STAT5B gain-of-function mutations have been frequently found in patients with T- and NK-cell neoplasms. STAT5BN642H represents the most frequently occuring STAT5B mutation. To investigate the molecular mechanism of STAT5BN642H-driven NK-cell leukemia, we performed RNA-Seq of liver derived FACS-sorted diseased N642HNK/NK and aged non-diseased control (Cre neg, GFPNK/NK), STAT5BNK/NK, N642HNK/NK NK cells.
Project description:The NK cell pool is composed of distinct NK cell subsets with divergent phenotypic and functional features. In order to determine whether DX5- and DX5+ NK cells from murine livers represent different NK cell subsets, DX5- and DX5+ liver NK cells of adult mice were respectively sorted for gene expression analysis using the Affymetrix GeneChip Mouse Genome 430 2.0 arrays. DX5-NK1.1+CD3- cells and DX5+NK1.1+CD3- cells were sorted from the liver of naive B6 wild-type mice. RNA of each sample was then extracted and hybridized on Affymetrix microarrays to detail differences between DX5- and DX5+ liver NK cells in gene expression.