Expansions of adaptive-like NK cells with a tissue-resident phenotype in human lung and blood
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE166654 | GEO | 2021/03/24
REPOSITORIES: GEO
Similar Datasets
Project description:Human lung tissue-resident NK cells (trNK cells) are likely to play important roles in viral infections, inflammation and cancer. However, knowledge about lung trNK cells is lacking but is fundamental for exploiting these cells in therapeutic approaches. Here we analysed the transcriptome of CD69+CD49a+CD103+CD16-CD56bright, CD69+CD49a+CD103-CD16-CD56bright, CD69+CD49a-CD103-CD16-CD56bright, CD69-CD49a-CD103-CD16-CD56bright, and CD56dimCD16+NKG2A+CD57- NK cells isolated from human lung.
| EGAS00001003544 | EGA
Project description:There is limited knowledge on the origin and development of the ample spectrum of human NK cells, particularly of specialized NK subsets. Here, we characterized the NK cell progeny of CD34+DNAM-1bright CXCR4+ precursors that reside in healthy bone marrow and circulate in the peripheral blood (PB) of patients with chronic infections/inflammation. including HIV, HCV or HCMV reactivation after HSC transplantation. Unlike conventional CD34+ precursors they rapidly differentiated in vitro into cytotoxic, IFNγ-secreting CD94/NKG2C+KIR+CD57+ maturing NK cell progenies with HCMV-inhibiting activity. Progeny characterization led also to identification of an additional new PB Lin-CD56-CD16+ precursor giving rise to the same CD94/NKG2C+KIR+CD57+ maturing NK cell progenies. Microarray analysis of NK cell progenies revealed a signature compatible with maturing adaptive NK cells. In vivo circulation of multiple common lymphocyte precursors with rapid development to NKG2C+ NK cell progeny is steadily occurring and may thus be a crucial resource for the prompt control of HCMV. We used microarray to compare the transcriptional profiles of human NKG2C+ NK cells derived from i) CD34+DNAM1brightCXCR4+ precursors, ii) Lin-CD34-CD16+CD56- precursors, iii) peripheral blood.
2020-12-31 | GSE136570 | GEO
Project description:The dataset contains RNAseq data from 5 subsets of NK cells isolated from human lung:
1) CD69+CD49a+CD103+CD16-CD56bright NK cells
2) CD69+CD49a+CD103-CD16-CD56bright NK cells
3) CD69+CD49a-CD103-CD16-CD56bright NK cells
4) CD69-CD49a-CD103-CD16-CD56bright NK cells
5) CD56dimCD16+NKG2A+CD57- NK cells
The dataset contains paired data for the subsets from 2 donors with 2 biological replicates/donor and subset.
| EGAD00001004850 | EGA
Project description:As a starting point for exploring potential differences in gene expression between conventional NK and FcRγ-NK cells, and to screen for genes that might contribute to the enhanced CD16 responsiveness of g-NK cells, we performed gene expression profiling studies on sorted samples of NK cells. NKG2C, NCR, and KIR surface receptors were used to separate FcRγ- NK and conventional NK cells. Indicated subsets of NK cells were sorted from 4 individual donors using a two-way sorter. RNA extracted from the sorted enriched samples were treated with Dnase and analyzed by DNA microarray (Agilent).
2015-02-20 | E-GEOD-66124 | biostudies-arrayexpress
Project description:As a starting point for exploring potential differences in gene expression between conventional NK and FcRγ-NK cells, and to screen for genes that might contribute to the enhanced CD16 responsiveness of g-NK cells, we performed gene expression profiling studies on sorted samples of NK cells. NKG2C, NCR, and KIR surface receptors were used to separate FcRγ- NK and conventional NK cells.
2015-02-20 | GSE66124 | GEO
Project description:Previous research on adaptive NK cells in rhesus macaques suffered from the lack of specific antibodies to differentiate between inhibitory CD94/NKG2A and stimulatory CD94/NKG2C heterodimeric receptors. Recently we reported an expansion of NKG2C receptor-encoding genes in rhesus macaques, but their expression and functional role on primary NK cells remained unknown due to this deficit. Thus, we established monoclonal antibodies 4A8 and 7B1 which show identical specificities and bind to both NKG2C-1 and NKG2C-2 but neither react with NKG2C-3 nor NKG2A on transfected cell lines. Using a combination of 4A8 and Z199 antibodies in multicolor flow cytometry we detected broad expression (4-73%) of NKG2C-1 and/or NKG2C-2 (NKG2C-1/2) on primary NK cells in rhesus macaques from our breeding colony. Stratifying our data to CMV-positive and CMV-negative animals, we noticed a higher proportion (23-73%) in primary NK cells expressing NKG2C-1/2 in CMV+ as compared to CMV- macaques (4-5%). These NKG2C-1/2-positive NK cells in CMV+ macaques are characterized by lower expression of IL12RB2, ZBTB16 and SH2D1B as well as high expression of IFN-gamma, indicating that antibody 4A8 detects CMV-associated adaptive NK cells. Single cell RNA seq data of 4A8-positive NK cells from a CMV-positive individual demonstrated that a high proportion of these adaptive NK cells transcribe in addition to NKG2C-1/2 also NKG2C-3, but interestingly NKG2A as well. Remarkably, NKG2C-1 and in particular NKG2C-2 have a higher affinity to Mamu-E as compared to NKG2A. Primary NK cells exposed to Mamu-E-expressing target cells displayed strong degranulation as well as IFN-gamma expression of 4A8+ adaptive NK cells of rhCMV+ animals that was not evident in rhCMV- animals. Thus, despite co-expression of inhibitory and stimulatory CD94/NKG2 receptors the higher number of different stimulatory NKG2C receptors and their higher binding avidity to Mamu-E outreach inhibitory signaling via NKG2A. These data demonstrate the evolutionary conservation of the CMV-driven development of NKG2C-positive adaptive NK cells with particular molecular signatures in primates and with changes in gene copy numbers and regulation and in ligand binding strength of NKG2C isotypes. Thus, rhesus macaques represent a suitable and valuable nonhuman primate animal model to study the CMV-NKG2C liaison in vivo.
2022-09-07 | GSE211613 | GEO
Project description:Natural killer cells are cytotoxic innate lymphoid cells that play an important role for early host defenses against infectious pathogens and surveillance against tumor growth and metastasis. In humans, NK cells may be divided in various subsets on the basis of the relative expression of the CD56 molecule and of the low-affinity FcγRIIIA CD16. In particular, the two main NK cell subsets are represented by the CD56bright CD16-/dull and the CD56dull CD16bright NK cells. A number of experimental evidences indicate that CD56bright and CD56dull NK cells represent different maturative stages of the NK cell developmental pathway. In an effort to identify NK cell miRNA signatures that may contribute to the NK cell-specific maturation program, we determined the miRNA profile of human NK cell subpopulations derived from peripheral blood samples of healthy donors. We identified multiple miRNAs that are differentially expressed in CD56bright CD16- and CD56dull CD16bright NK cells. Among these, we found a few miRNAs with a consistent differential expression in the two NK cell subsets, and with an intermediate expression in the CD56brightCD16dull NK cell subset, representing a transitional step of maturation of NK cells. Our data have been confirmed by both quantitative real-time PCR and multivariate analysis. These analyses allowed us to establish the existence of a miRNA signature able to discriminate the two main NK cell subsets, regardless of their surface phenotype. In addition, by analyzing the putative targets of representative miRNAs we show that miR-146a-5p, that displays a significant up-regulation in CD56bright as compared to CD56dull NK cells, may be involved in the regulation of killer Ig-like receptor (KIR) expression. These findings may contribute to a better understanding of the physiologic significance of miRNAs in the regulation of NK cell development/function. In addition, our results suggest that miR-146a-5p targeting, resulting in KIR down-regulation, may be exploited as a tool to generate/increment the effect of NK KIR-mismatching against HLA class I+ tumor cells and thus to improve the NK-mediated anti-tumor activity.
2018-11-06 | GSE116743 | GEO
Project description:NK cells are lymphocytes that provide a first defense against viral infections and cancer. They act (i) cytotoxic by killing virus-infected and tumorigenic cells and (ii) immune regulatory by releasing cytokines and chemokines. These innate immune cells are commonly further classified as CD56bright and CD56dim NK cells. Former studies confirmed immune regulatory CD56bright NK cells as progenitors of cytotoxic CD56dim NK cells. CD57 was previously described as T cell marker for senescence and terminal differentiation. Recent studies detected CD57+ and CD57- NK cells among the CD56dim NK cell population and suggested a fully mature developmental status for CD57+ NK cells. The recent NK cell maturation model includes CD34+ hematopoietic stem cells (HSC), which develop into CD56bright NK cells, later into CD56dimCD57- and finally into terminally maturated CD56dimCD57+ (1) (2) (3). The molecular mechanisms of human NK cell differentiation and maturation remain unknown to this date. We performed for the first time a proteomic analysis of these distinct developmental stages of human primary NK cells, isolated from overall 10 healthy human blood donors. CD56bright NK cells versusCD56dim and CD56dimCD57- versus CD56dimCD57+ NK cells were analyzed by using quantitative peptide sequencing, which revealed individual protein signatures (3400 proteins) of these different NK cell developmental stages. Notably, our data support the current NK cell differentiation model by highlighting both strong distinctions between CD56dim/bright NK cells and close relationships between CD57+/- NK cells on the proteomic level. Among the most prominent and conserved regulated proteins, we detected myosin IIa, Calvasculin and Calcyclin with very similar expression patterns. We investigated their sub-cellular localization and observed specific recruitment- and accumulation-events at the NK cell immunological synapse (NKIS) after NK activation.
2013-01-23 | PRD000666 | Pride
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:CD8+ T cells, critical mediators of adaptive immunity, may also exhibit innate-like properties, such as surface expression of NKG2C, an activating receptor typically associated with natural killer (NK) cells. We demonstrate that, similar to NK cells, NKG2C+TCRαβ+CD8+ T cells are associated with prior HCMV exposure. In addition to expressing several NK cell markers (CD56, KIR), NKG2C+CD8+ T cells are oligoclonal and do not upregulate PD1 despite chronic activation. Furthermore, NKG2C+CD8+ T cells from some individuals exhibit high effector function against leukemia cells and HCMV-infected fibroblasts, dictated by NKG2C and TCR specificity. Importantly, we observe that co-triggering of CD3 and NKG2C results in increased degranulation and IFN-γ production by NKG2C+CD8+ T cells in an additive fashion. Transcriptomic analysis reveals that the transcription factor BCL11B, a regulator of T cell developmental fate, is significantly down-modulated in NKG2C+CD8+ T cells when compared to conventional NKG2C-CD8+ T cells. BCL11B deletion in conventional CD8 T cells results in the emergence of a CD56+CD94+DAP12+NKG2C+CD45RA+CCR7-PD1-/low T cell population with activity against HLA-E+ targets. Given their intrinsic capacity to recognize diseased cells coupled with lack of PD-1 upregulation despite chronic stimulation, NKG2C+CD8+ T cells represent a novel lymphocyte population that straddles the boundary between innate and adaptive immunity, presenting an attractive alternative for cellular therapy, including CAR T-based therapies.
2021-10-14 | GSE179981 | GEO