A discrete subset of epigenetically primed human NK cells mediates antigen-specific immune responses
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA665413 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12703516.fastq.gz | Fastqsanger.gz | |||
| SRR12703517.fastq.gz | Fastqsanger.gz | |||
| SRR12703518.fastq.gz | Fastqsanger.gz | |||
| SRR12703519.fastq.gz | Fastqsanger.gz | |||
| SRR12703520.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 50 |
Similar Datasets
Project description:Adaptive features of natural killer (NK) cells have been reported in various species with different underlying mechanisms. It is unclear, however, which NK cell populations are capable of mounting antigen-specific recall responses, and how such functions are regulated at the molecular level. Here we identify and characterize a discrete population of CD49a+CD16- NK cells in the human liver that display increased epigenetic potential to elicit memory responses and has the functional properties to exert antigen-specific immunity on the skin as an effector site. Integrated chromatin-based epigenetic and transcriptomic profiling revealed unique characteristics of hepatic CD49a+CD16- NK cells when compared to conventional CD49a-CD16+ NK cells thereby defining active genomic regions and molecules underpinning distinct NK cell reactivity. In contrast to conventional NK cells, our results suggest adaptive CD49a+CD16- NK cells to be able to bypass the KIR receptor-ligand system upon antigen-specific stimulation. Furthermore, these cells were highly migratory towards chemokine gradients expressed in epicutaneous patch test lesions as an effector site of adaptive immune responses of the skin. These results define pathways operative in human antigen-specific memory NK cells and provide a roadmap for harnessing this NK cell subset for specific therapeutic or prophylactic vaccine strategies.
2020-10-15 | GSE158485 | GEO
Project description:Adaptive features of natural killer (NK) cells have been reported in various species with different underlying mechanisms. It is unclear, however, which NK cell populations are capable of mounting antigen-specific recall responses and how such functions are regulated at the molecular level. Here, we identify and characterize a discrete population of CD49a+CD16- NK cells in the human liver that displays increased epigenetic potential to elicit memory responses and has the functional properties to exert antigen-specific immunity in the skin as an effector site. Integrated chromatin-based epigenetic and transcriptomic profiling revealed unique characteristics of hepatic CD49a+CD16- NK cells when compared with conventional CD49a-CD16+ NK cells, thereby defining active genomic regions and molecules underpinning distinct NK cell reactivity. In contrast to conventional NK cells, our results suggest that adaptive CD49a+CD16- NK cells are able to bypass the KIR receptor-ligand system upon antigen-specific stimulation. Furthermore, these cells were highly migratory toward chemokine gradients expressed in epicutaneous patch test lesions as an effector site of adaptive immune responses in the skin. These results define pathways operative in human antigen-specific adaptive NK cells and provide a roadmap for harnessing this NK cell subset for specific therapeutic or prophylactic vaccine strategies.
| S-EPMC7615005 | biostudies-literature
Project description:is involved in the formation of immune signaling complexes. To date only limited and moreover 35 conflicting data exist regarding the role of ADAP in NK cells. To extend existing knowledge we 36 investigated ADAP-dependency of NK cells in the context of in vivo infection with the intracellular 37 pathogen Listeria monocytogenes (Lm). Ex vivo analysis of infection-primed NK cells revealed 38 impaired expression of IFN-γ and chemokines as well as impaired cytotoxic capacity in NK cells 39 lacking ADAP as indicated by reduced CD107a surface expression and inefficient perforin 40 production. However, ADAP-deficiency had no global effect on NK cell morphology or intracellular 41 distribution of CD107a-containing vesicles. Proteomic definition of ADAPko and wild type NK cells 42 did not uncover obvious differences in protein composition during the steady state and moreover, 43 similar early response patterns were induced in NK cells upon infection independent of the genotype. 44 In line with protein network analyses that suggested an altered migration phenotype in naïve 45 ADAPko NK cells, in vitro migration assays uncovered significantly reduced migration of both naïve 46 as well as infection-primed ADAPko NK cells compared to wild type NK cells. We propose that this 47 migration defect might account at least in part for the fact that during in vivo infection significantly 48 lower numbers of ADAPko NK cells accumulate in the spleen i.e. the site of infection. In conclusion, 49 we show here that during systemic Lm infection in mice ADAP is essential for efficient cytokine and 50 chemokine production, cytotoxic capacity and migration of NK cells.
2020-05-27 | PXD016305 | Pride
Project description:Rheumatoid Arthritis circulating CD14+ monocytes are epigenetically primed [ChIP-seq]
| PRJNA1248776 | ENA
Project description:TNF is a homeostatic regulator of distinct epigenetically primed human osteoclast precursors
| PRJNA640824 | ENA
Project description:We identified a unique NK cell subset (DN NK) in the spleen. These cells displayed an immature phenotype and could develop into mature conventional NK (cNK) cells.
2019-07-15 | GSE133950 | GEO
Project description:The cell lineage origin of interferon-producing killer dendritic cells (IKDC), which exhibit prominent anti-tumoral activity, has been subject to debate. Although IKDC were first described as a cell type exhibiting both pDC and NK cell properties, the current view reflects that IKDC merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relationship of B220+ NK cells with regards to other NK cell subsets. We surprisingly find that, upon adoptive transfer, B220- NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220+ NK cells are activated NK cells in vivo. Moreover, we unequivocally demonstrate that B220+ NK cells are highly proliferative and differentiate into mature NK cells upon in vivo adoptive transfer. Additional phenotypic, functional and transcriptional characterizations further define B220+ NK cells as immediate precursors to mature NK cells. By analogy to pre-B cells and pre-DC, we propose that B220+ NK cells should be renamed pre-NK cells. The characterization of these novel attributes to pre-NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies. Total RNA from B220+ NK cells compared to total RNA from CD27- and CD27+ NK cell subsets all isolated ex vivo from the spleen of B6.Rag-/-. Triplicatas were analysed.
2012-05-14 | E-GEOD-34237 | biostudies-arrayexpress
Project description:TSLPR expression marks a functionally discrete subset of human monocytes elicited by TLR4 activation.
| PRJEB15099 | ENA
Project description:Human Natural Killer (NK) cells comprise two main subsets, CD56bright and CD56dim cells, that differ in function, phenotype and tissue localization. To further dissect the heterogeneity of CD56dim cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56dim CD62L+ cells. Indeed, only these cells combine the ability to produce interferon (IFN)-gamma after cytokines and proliferate in vivo during viral infection with the capacity to kill and produce cytokines upon engagement of activating receptors. Therefore, CD56dim CD62L+ cells represent a unique subset of polyfunctional NK cells. Ex vivo analysis of their function, phenotype, telomere length, frequencies during ageing as well as transfer experiments of NK cell subsets into immunodeficient mice suggest that CD56dim CD62L+ cells represent an intermediate stage of NK cell maturation, which after restimulation can accomplish multiple tasks and further develop into terminally differentiated effectors. Gene expression profiles of FACSAria sorted CD3- CD56bright CD62L+, CD3- CD56dim CD62L+ and CD3- CD56dim CD62L- NK cells from human peripheral blood of three donors were compared using Affymetrix GeneChip Human Genome HG-U133_Plus_2. After total RNA extraction, reverse transcription, cDNA extraction, the biotinylated cRNA was transcribed, fragmented, and 15 µg cRNA hybridized in triplicates for each of the three groups to the GeneChip arrays. Group1: CD3- CD56bright CD62L+,.Group2: CD3- CD56dim CD62L+, Group3: CD3- CD56dim CD62L-. Lists of differentially regulated genes were created using High Performance Chip Data Analysis (HPCDA) with Bioretis database (http://www.bioretis-analysis.de). Worldwide data sharing is possible via Bioretis, please ask the authors.
2010-05-28 | E-GEOD-21774 | biostudies-arrayexpress
Project description:In this study we performed single-cell RNA sequencing on 7000 negatively enriched fresh NK and progenitor cells from one healthy bone marrow donor, that were pre-labeled with oligonucleotide-conjugated antibodies against CD34, CD117, CD56 and CXCR6. A new CD56dimGzmK+ subset was identified that shared features with CD56bright and CD56dimGzmK- NK cells based on transcriptome, phenotype (NKG2AhighCD16lowKLRG1highTIGIThigh) and functional analysis in bone marrow and blood, supportive for an intermediate subset. Pseudotime analysis positioned CD56bright, CD56dimGzmK+ and CD56dimGzmK- cells in one differentiation trajectory, while ltNK cells were separated in a distinct lineage. Integrative analysis with bone marrow cells from the human cell atlas did not demonstrate a developmental connection between CD34+ progenitor and NK cells, implicating that bone marrow is not a site of active NK cell development.
2022-10-01 | GSE199411 | GEO