Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Natural killer cell receptor expressing B cells: a distinct but rare subset of innate immune cells in rhesus macaques

ABSTRACT: Natural killer-like B (NKB) cells are unique innate immune cells that express both natural killer (NK) and B cell markers. They act as first responders by secreting IL-18 upon infection, thus inducing the critical cascade of innate and adaptive immune cell infiltration and activation. However, limited research exists on the role of NKB cells in homeostasis, and infection in primates. Therefore, we investigated the signaling and trafficking proteome, in situ localization and transcriptome of NKB cells in comparison to conventionally defined NK and B cells. Intracellular signaling proteins and trafficking markers were expressed differentially on naïve NKB characterized by high expression of CD62L and Syk, and low expression of CD69, a4b7, FcRg, Zap70, and CD3z which were more similar to B cells than NK cells. CD20+NKG2a/c+ NKB cells were identified in spleen, mesenteric lymph nodes (MLN), colon, jejunum, and liver of naïve RM by tissue imaging with NKB cell counts concentrated in spleen and MLN. Transcriptomic analysis of naïve splenic NKB cells by scRNAseq showed that NKB cells undergo somatic hypermutation and express Ig receptors, similar to B cells. While only 15% of sorted NKB population showed transcript expression of both KLRC1 (NKG2A) and MS4A1 (CD20), cells expressing KLRC1, MS4A1and IgH/IgL transcripts were only 5%. However, we observed expanded NKB frequencies in gut mucosa as early as 35 days and in buccal mucosa as early as 14 days post-SIV infection using an RM model of HIV infection, thus indicating NKB cells, though infrequent, could have potential roles to play in mucosal infections.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE263399 | GEO | 2024/04/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNAseq analysis of NKG2A-knockout versus wildtype expanded human NK cells

Project description:Checkpoint blockage has revolutionized cancer treatment. NKG2A is an inhibitory receptor expressed by cytotoxic lymphocytes, including NK cells. In contrast to other checkpoint inhibitory antibodies, anti-NKG2A antibodies have shown only limited success. Here, we designed a Cas9-based strategy to delete KLRC1 from human NK cells. Electroporation of KLRC1-targeting Cas9-RNP efficiently eliminated NKG2A expression from primary human NK cells. NKG2A-deficient NK cells showed normal proliferation, only minor transcriptional changes related to enhanced NK cell activation and maintained their phenotype and licensing status. Genetic deletion of NKG2A fully bypassed HLA-E inhibition and further enhanced NK cell activity against various tumor cell lines, thereby outperforming anti-NKG2A antibodies. In combination with antibody-coating of tumor cells to induce antibody-dependent cellular cytotoxicity, genetic deletion of NKG2A independently promoted cytotoxicity. Thus, Cas9-mediated targeting of NKG2A is an effective way to target this important inhibitory checkpoint. This technique is easily amenable to adoptive cell therapy in the clinical setting, where NKG2A deletion will promote anti-tumor responses and may help NK cells to better infiltrate and persist in an inhibitory tumor microenvironment.

2021-09-01 | GSE178566 | GEO

Expression data from WT and Klrc1-/- CD8+ T cells

Project description:CD8+ T cells and NK cells protect from viral infections by killing virally-infected cells and secreting interferon-g. Several inhibitory receptors limit the magnitude and duration of these anti-viral responses. We used microarrays to assess the transcriptome of ectromelia virus (ECTV) specific CD8+ T cells that genetically lack one such receptor, NKG2A, which is encoded by Klrc1. NaÃ¯ve or ECTV-specific CD8+ T cells were sorted directly into RLT buffer. RNA was then extracted, processed, and hybridized to Affymetrix arrays.

2015-11-07 | E-GEOD-74780 | biostudies-arrayexpress

Expression data from WT and Klrc1-/- CD8+ T cells

2015-11-07 | GSE74780 | GEO

CITE-seq of CAR-NK cells

Project description:Primary chimeric antigen receptor (CAR) natural killer (NK) cells show strong cytotoxic efficacy against acute myeloid leukemia (AML) in vivo. However, NK cell-mediated tumor killing is often impaired by tumor-mediated immune cell inactivation. Here, we report a novel strategy to overcome NK cell inhibition caused by the immune checkpoint NKG2A, which interacts with HLA-E expressed on AML blasts. We generated AML-specific CD33-directed CAR (CAR33)-KLRC1ko-NK cells with CRISPR/Cas9-based gene editing of the NKG2A-encoding KLRC1 gene. Single-cell multi-omic analyses revealed a higher proportion of activated cells in CAR33-NK- and CAR33-KLRC1ko-NK pools, which were preserved following AML-cell contact. This activated state of the CAR33-KLRC1ko-NK cells has been translated into improved antileukemic activity in vitro and in vivo against AML cell lines and primary blasts. This dual modification of primary NK cells has the potential to bypass the suppressive effect not only of AML but also in a broad range of other cancer identities.

2024-07-16 | GSE221552 | GEO

Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells

Project description:A key mechanism of tumor resistance to immune cells is mediated by expression of peptide-loaded HLA-E in tumor cells, which suppresses natural killer (NK) cell activity via ligation of the NK inhibitory receptor CD94/NKG2A. To bypass HLA-E inhibition, we developed a way to generate highly functional NK cells lacking NKG2A. Constructs containing a single-chain variable fragment derived from an anti-NKG2A antibody were linked to endoplasmic reticulum-retention domains. After retroviral transduction in human peripheral blood NK cells, these NKG2A Protein Expression Blockers (PEBLs) abrogated NKG2A expression. The resulting NKG2Anull NK cells had higher cytotoxicity against HLA-E-expressing tumor cells.

2019-05-17 | GSE127081 | GEO

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort2]

Project description:Unlike HIV infection, which progresses to AIDS absent suppressive anti-retroviral therapy (ART), nonpathogenic infections in natural hosts, such African green monkeys (AGMs), are characterized by a lack of gut microbial translocation and robust secondary lymphoid Natural Killer (NK) cell responses resulting in absence of chronic inflammation and limited SIV dissemination in lymph nodes (LN) B-cell-follicles, respectively. In a pathogenic infection model (i.e. ART-treated, SIVmac239-infected rhesus macaques; RMs), sequential Interleukin (IL)-21 and interferon (IFN)-alpha therapy generated terminally-differentiated blood NK cells (NKG2a/clowCD16+) with potent HLA-E-restricted activity in response to SIV-ENV peptides in contrast to control RMs, where less differentiated, IFN-gamma+ NK cells predominated. The frequency and cytolytic activity of NKG2a/clowCD16+ NK cells correlated with a reduction of replication-competent SIV in LN during ART and viral rebound delay following analytical treatment interruption. These data demonstrate that AGM-like NK cell differentiation profiles can be rescued in RMs to promote viral clearance in tissues.

2021-02-22 | GSE163441 | GEO

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort1]

2021-02-22 | GSE163440 | GEO

IL-21 and IFNalpha therapy rescues terminally-differentiated NK cells and limit SIV reservoir in ART-treated macaques [cohort3]

2021-02-22 | GSE163442 | GEO

Developing enhanced immunotherapy using NKG2A knockout human pluripotent stem cell-derived NK cells

Project description:Cancer immunotherapy is gaining increasing attention. However, immune checkpoints are exploited by cancer cells to evade anti-tumor immunotherapy. Here, we knocked out NKG2A, an immune checkpoint expressed on natural killer (NK) cells, in human pluripotent stem cells (hPSCs) and differentiated these hPSCs into NK (PSC-NK) cells. We show that NKG2A knockout (KO) enhances the anti-tumor and anti-viral capabilities of PSC-NK cells. NKG2A KO endows PSC-NK cells with higher cytotoxicity against HLA-E-expressing glioblastoma (GBM) cells, leukemia cells, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected cells in vitro. The NKG2A KO PSC-NK cells also exerted potent anti-tumor activity in vivo, leading to substantially suppressed tumor progression and prolonged survival of tumor-bearing mice in a xenograft GBM mouse model. These findings underscore the potential of PSC-NK cells with immune checkpoint KO as a promising cell-based immunotherapy. The unlimited supply and ease of genetic engineering of hPSCs makes genetically engineered PSC-NK an attractive option for easily accessible "off-the-shelf" cancer immunotherapy.

2024-10-18 | GSE241039 | GEO

ADAP promotes effector cytokine release, degranulation and migration 1 of NK cells primed during in vivo Listeria monocytogenes infection in 2 mice

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data