Expression data from activated NK cells [miRNA]
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ABSTRACT:
ORGANISM(S): synthetic construct Homo sapiens
PROVIDER: GSE50839 | GEO | 2014/09/09
SECONDARY ACCESSION(S): PRJNA219134
REPOSITORIES: GEO
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Project description:Natural Killer (NK) cells present natural cytotoxicity against tumor cells, although their activity is increased after activation. NK cell activation depends on a complex intracellular signaling process mediated by activating and inhibitory receptors and the functional outcome depends on the integration of the activating and inhibitory signals received. Soluble cytokines and/or ligands on target cells bind the NK cell receptors, and hence, influence the final NK cell response: attack versus ignorance. We used microarrays to detail the global programme of gene expression underlying NK cell activation by IL-2, a MHC-I-deficient target cell (K562)+IL-2 and an EBV-target cell (R69).
2014-09-09 | GSE50838 | GEO
Project description:Natural Killer (NK) cells present natural cytotoxicity against tumor cells, although their activity is increased after activation. NK cell activation depends on a complex intracellular signaling process mediated by activating and inhibitory receptors and the functional outcome depends on the integration of the activating and inhibitory signals received. Soluble cytokines and/or ligands on target cells bind the NK cell receptors, and hence, influence the final NK cell response: attack versus ignorance. We used microarrays to detail the global programme of gene expression underlying NK cell activation by IL-2, a MHC-I-deficient target cell (K562)+IL-2 and an EBV-target cell (R69). PBLs from 4 different donors were activated by 100 U/ml IL-2; K562+IL-2 or R69 cells. After 5 days we obtained RNA and miRNA from naïve NK cells or from NK cells activated with the above mentioned stimuli, with more than 90% of purity. The 16 RNA samples were used to generate cDNA libraries that were hybridized on Human Gene 1.1ST arrays (Affymetrix) and analyzed with the Affymetrix Gene Chip Command Console Software v3.0 (AGCC 3.0, Affymetrix®) and the Expression Console Software v1.1 (Affymetrix®).
2014-09-09 | E-GEOD-50838 | biostudies-arrayexpress
Project description:Natural Killer (NK) cells present natural cytotoxicity against tumor cells, although their activity is increased after activation.NK cell activation depends on a complex intracellular signaling process mediated by activating and inhibitory receptors and the functional outcome depends on the integration of the activating and inhibitory signals received. Soluble cytokines and/or ligands on target cells bind the NK cell receptors, and hence, influence the final NK cell response: attack versus ignorance. We used microarrays to detail the global programme of gene expression underlying NK cell activation by IL-2, a MHC-I-deficient target cell (K562)+IL-2 and an EBV-target cell (R69). PBLs from 4 different donors were activated by 100 U/ml IL-2; K562+IL-2 or R69 cells. After 5 days we obtained RNA and miRNA from naïve NK cells or from NK cells activated with the above mentioned stimuli, with more than 90% of purity. The 16 RNA samples were used to generate cDNA libraries that were hybridized on Human Gene 1.1ST arrays (Affymetrix) and analyzed with the Affymetrix Gene Chip Command Console Software v3.0 (AGCC 3.0, Affymetrix®) and the Expression Console Software v1.1 (Affymetrix®).
2014-09-09 | E-GEOD-50839 | biostudies-arrayexpress
Project description:To discriminate between our own cells and those of a pathogen, natural killer cells are armed with inhibitory and activating immune receptors. The balance in signalling mediated by these receptors determines whether an NK cell is activated to destroy a target cell. In some cases, such as the KIRs, immune receptors are found in pairs, with inhibitory and activating receptors containing nearly identical extracellular ligand-binding domains, coupled to different intracellular signalling domains1. Previous studies have shown that RIFINs, displayed on surfaces of Plasmodium falciparum-infected erythrocytes, can bind to inhibitory immune receptors and dampen NK cell activation2,3, reducing parasite killing. However, no pathogen-derived ligand has been identified for any activating receptor. Here, we identify a clade of RIFINs that bind to inhibitory immune receptor KIR2DL1 more strongly than KIR2DL1 binds the human ligand, MHC class I. We demonstrate that this interaction mediates inhibitory signaling and suppresses the activation of KIR2DL1-expressing NK cells. We show that KIR2DL1-binding RIFINs are abundant in field-isolated strains from both Africa and Asia and reveal how two RIFINs bind KIR2DL1. We also demonstrate that the RIFIN binding surface of KIR2DL1 is conserved in the cognate activating immune receptor KIR2DS1. We find that KIR2DL1-binding RIFINs can also bind to KIR2DS1, resulting in activation of KIR2DS1-expressing NK cells. This study demonstrates for the first time that activating KIRs can recruit natural killer cells to target a pathogen and reveals a potential role for activating immune receptors in control of malaria infection
2025-01-15 | GSE286478 | GEO
Project description:Natural killer (NK) cells have differential expression of inhibitory and activating receptors. NK cells that express inhibitory receptors with high binding affinity to self are considered licensed and normally functional cells, while those with low affinity are unlicensed are considered hyporesponsive. Microarray analysis was performed to better understand gene expression differences between these two subpopulations of NK cells after culturing the NK cells with IL-2 from splenocytes isolated from C57BL/6 mice and then sorting for CD3-CD122+Ly49G2+Ly49C/I- or CD3-CD122+Ly49G2-Ly49C/I+. Gene fold expression differences were compared between the Ly49G2+ and Ly49C/I+ NK cells to better understand the functional roles and characterisitics of these cells. A total of 6 samples were analyzed, 3 for the CD3-CD122+Ly49G2+Ly49C/I- NK cells and 3 for the CD3-CD122+Ly49G2-Ly49C/I+. Samples were obtained from C57BL/5 splenocytes that were T cells depleted through anti-Thy1.2 and complement mediated depletion and cultured for 7 days with IL-2. Fold changes greater than 1.5 were recorded.
2014-09-01 | E-GEOD-56662 | biostudies-arrayexpress
Project description:Liver transplantation (LT) is a definitive treatment for end-stage liver disease and hepatocellular cancer. As donor-recipient HLA matching is not employed, there is potential for natural killer (NK) cell-mediated alloreactivity. Here we report that recipient NK cells exhibit a downregulated phenotype with reduced expression of activating receptors NKp30 and NKp46. We found associated hypofunctionality, with impaired NK cell cytotoxicity, degranulation and IFN-gamma production. Gene expression analysis using microarray and quantitative PCR identified significant downregulation of STAT-4 in LT with associated reduction in miR-155, a microRNA target of STAT-4 and a key regulator of NK differentiation. These data indicate that LT induces recipient NK cell tolerance through altered peripheral maturation at a step prior to the acquisition of inhibitory receptors for HLA class I.
2014-02-01 | E-MTAB-2132 | biostudies-arrayexpress
Project description:Natural Killer cells (NK), a major constituent of innate immune system, have the ability to kill the transformed and infected cells without prior sensitization; can be put to immunotherapeutic use against various malignancies. NK cells discriminate between normal cells and transformed cells via a balance of inhibitory and activating signals induced by interactions between NK cell receptors and target cell ligands. Present study investigates whether expansion of NK cells could augment their anti-myeloma (MM) activity. For NK cell expansion, peripheral blood mononuclear cells from healthy donors and myeloma patients were co-cultured with irradiated K562 cells transfected with 4-1BBL and membrane-bound IL15 (K562-mb15-41BBL). A genome-wide profiling approach was performed to identify gene expression signature in expanded NK (ENK) cells and non-expanded NK cells isolated from healthy donors and myeloma patients. A specific set of genes involved in proliferation, migration, adhesion, cytotoxicity, and activation were up regulated post expansion, also confirmed by flow cytometry. Exp-NK cells killed both allogeneic and autologous primary MM cells more avidly than non-exp-NK cells in vitro. Multiple receptors, particularly NKG2D, natural cytotoxicity receptors, and DNAM-1 contributed to target lysis, via a perforin mediated mechanism. In summary, vigorous expansion and high anti-MM activity both in vitro and in vivo provide the rationale for testing exp-NK cells in a clinical trial for high risk MM. Differential gene expression profile in expanded natural killer (ENK) cells and non-expanded natural killer (NK) cells from healthy donors and myeloma patients Eight healthy donor and eight myeloma patients were used in the study. Non-expanded natural killer (NK) cells were isolated from PBMCs of healthy donors and myeloma patients. Expanded natural killer (ENK) cells were generated from same set of samples as mentioned in expansion protocol. All ENK and NK cells were used for gene expression profiling.
2011-03-08 | E-GEOD-27838 | biostudies-arrayexpress
Project description:Natural killer (NK) cells have differential expression of inhibitory and activating receptors. NK cells that express inhibitory receptors with high binding affinity to self are considered licensed and normally functional cells, while those with low affinity are unlicensed are considered hyporesponsive. Microarray analysis was performed to better understand gene expression differences between these two subpopulations of NK cells after culturing the NK cells with IL-2 from splenocytes isolated from C57BL/6 mice and then sorting for CD3-CD122+Ly49G2+Ly49C/I- or CD3-CD122+Ly49G2-Ly49C/I+. Gene fold expression differences were compared between the Ly49G2+ and Ly49C/I+ NK cells to better understand the functional roles and characterisitics of these cells.
2014-09-01 | GSE56662 | GEO
Project description:We report here the design of new antibody-based natural killer cell engager therapeutics (ANKET), single tetraspecific molecules engaging the NK cell activating receptors NKp46 and CD16, the β chain of the interleukin-2 receptor (IL-2R) and a tumor-associated antigen (TAA).
2022-10-05 | GSE214378 | GEO
Project description:Natural Killer cells (NK), a major constituent of innate immune system, have the ability to kill the transformed and infected cells without prior sensitization; can be put to immunotherapeutic use against various malignancies. NK cells discriminate between normal cells and transformed cells via a balance of inhibitory and activating signals induced by interactions between NK cell receptors and target cell ligands. Present study investigates whether expansion of NK cells could augment their anti-myeloma (MM) activity. For NK cell expansion, peripheral blood mononuclear cells from healthy donors and myeloma patients were co-cultured with irradiated K562 cells transfected with 4-1BBL and membrane-bound IL15 (K562-mb15-41BBL). A genome-wide profiling approach was performed to identify gene expression signature in expanded NK (ENK) cells and non-expanded NK cells isolated from healthy donors and myeloma patients. A specific set of genes involved in proliferation, migration, adhesion, cytotoxicity, and activation were up regulated post expansion, also confirmed by flow cytometry. Exp-NK cells killed both allogeneic and autologous primary MM cells more avidly than non-exp-NK cells in vitro. Multiple receptors, particularly NKG2D, natural cytotoxicity receptors, and DNAM-1 contributed to target lysis, via a perforin mediated mechanism. In summary, vigorous expansion and high anti-MM activity both in vitro and in vivo provide the rationale for testing exp-NK cells in a clinical trial for high risk MM. Differential gene expression profile in expanded natural killer (ENK) cells and non-expanded natural killer (NK) cells from healthy donors and myeloma patients
2011-03-08 | GSE27838 | GEO