Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ionomycin Treatment Renders NK cells Hyporesponsive

ABSTRACT: Natural killer cells are cytotoxic lymphocytes important in immune responses to cancer and multiple pathogens. However, chronic activation of NK cells can induce a hyporesponsive state. The molecular basis of the mechanisms underlying the generation and maintenance of this hyporesponsive state are unknown, thus an easy and reproducible mechanism able to induce hyporesponsiveness on human NK cells would be very useful to gain understanding of this process. Human NK cells treated with ionomycin lose their ability to degranulate and secrete IFN-γ in response to a variety of stimuli, but IL-2 stimulation can compensate these defects. Apart from reductions in the expression of CD11a/CD18, no great changes were observed in the activating and inhibitory receptors expressed by these NK cells, however their transcriptional signature is different to that described for other hyporesponsive lymphocytes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE79118 | GEO | 2017/01/29

SECONDARY ACCESSION(S): PRJNA314976

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Ionomycin Treatment Renders NK Cells Hyporesponsive.

Project description:Natural killer cells are cytotoxic lymphocytes important in immune responses to cancer and multiple pathogens. However, chronic activation of NK cells can induce a hyporesponsive state. The molecular basis of the mechanisms underlying the generation and maintenance of this hyporesponsive condition are unknown, thus an easy and reproducible mechanism able to induce hyporesponsiveness on human NK cells would be very useful to gain understanding of this process. Human NK cells treated with ionomycin lose their ability to degranulate and secrete IFN-γ in response to a variety of stimuli, but IL-2 stimulation can compensate these defects. Apart from reductions in the expression of CD11a/CD18, no great changes were observed in the activating and inhibitory receptors expressed by these NK cells, however their transcriptional signature is different to that described for other hyporesponsive lymphocytes.

| S-EPMC4805247 | biostudies-literature

Homo sapiens

Project description:Ionomycin Treatment Renders NK cells Hyporesponsive

| PRJNA314976 | ENA

Differential roles of ROR gamma-t in the development of NKp46+ spleen (LTIL) cells and NKp46+ NK cells in gut and skin

Project description:Natural killer (NK) cells are NKp46+CD3- lymphocytes that can perform granule-dependent cytotoxicity and produce interferon-gamma, when isolated from blood, lymphoid organs, lung, liver and uterus. Here we identify in dermis, gut lamina propria and cryptopatches, very distinct populations of NKp46+CD3- cells with reduced ability to degranulate and to produce interferon-gamma. In gut, the transcription factor RORgamma-t and CD127 (IL-7R alpha) defined a novel subset of NKp46+CD3- that is reminiscent of lymphoid tissue inducer (LTi)-like cells. Gut ROR gamma t+NKp46+ cells produced IL-22 in contrast to ROR-gamma t-independent lamina propria and dermis NK cells. These data show that LTi-like cells and NK cells share unanticipated similarities and reveal the heterogeneity of NKp46+CD3- cells in innate immunity, lymphoid organization and local tissue repair.

2008-10-22 | GSE13151 | GEO

Expression data from CD4+IL-4gfp+ Th2 cells isolated from BALB/c IL-4gfp 4get mice infected with the filarial nematode Litomosoides sigmodontis.

Project description:Litomosoides sigmodontis is parasitic filarial nematode that can infect mice, and is used as a murine model for human filariasis. Type 2 immune responses are protective, but infection is typically chronic due to a combination of immune suppression by the parasite and immune regulation by the host dampening protective Type 2 immunity. We have shown that the CD4+ Th2 cells develop an intrinsically hyporesponsive or dysfunctional phenotype between day 20 and 60 of infection, denoted by an impaired ability to proliferate and produce Th2 cytokines. The hyporesponsive phenotype is PD-1/PD-L2 dependent, and impairs parasite killing (van der Werf et al. 2013. PloS Path. e1003215). This study aimed to investigate the mRNA expression of the intrinsically-hyporesponsive Th2 cells to determine the mechanisms by which they become dysfunctional, and to test whether Th2 cell intrinsic hyporesponsiveness has similarities with other forms of T cell-intrinsic regulation such as exhaustion, tolerance or anergy.

2019-11-25 | GSE114308 | GEO

Acetate promotes T cell effector function during glucose restriction [ChIP-seq]

Project description:Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation to the surrounding microenvironment is therefore key for maintaining appropriate cell function. For instance, cancer cells use acetate as a substrate alternative to glucose to fuel metabolism and growth. Here we show that acetate rescued effector function in glucose-restricted CD8+ T cells. Mechanistically, acetate promoted histone acetylation and chromatin accessibility, and enhanced IFN-γ gene transcription and cytokine production in an acetyl-CoA synthetase (ACSS)-dependent manner. Ex vivo acetate treatment increased IFN-γ production by exhausted T cells, while reducing ACSS expression in T cells impaired IFN-γ production by tumor-infiltrating lymphocytes and tumor clearance. Thus, hyporesponsive T cells can be epigenetically remodeled and reactivated by acetate, suggesting that pathways regulating the use of substrates alternative to glucose could be therapeutically targeted to promote T cell function during cancer.

2019-05-14 | GSE128593 | GEO

Acetate promotes T cell effector function during glucose restriction [ATAC-seq]

2019-05-14 | GSE128592 | GEO

Acetate promotes T cell effector function during glucose restriction [RNA-seq]

2019-05-14 | GSE128591 | GEO

b2 integrins inhibit suppressor of cytokine signaling but also inflammation-associated gene expression in dendritic cells (DC), in line with attenuated T cell activation in autoimmune encephalomyelitis

Project description:Heterodimeric b2 integrin surface receptors (CD11a-d/CD18) are specifically expressed by leukocytes that contribute to pathogen uptake, cell migration, immunological synapse formation and cell signaling. In human, loss of CD18 expression results in leukocyte adhesion deficiency syndrome (LAD-)1, largely characterized by recurrent severe infections.. All available mouse models display a constitutive and ubiquitous knockout of either a or the common b2 (CD18) subunit, which hampers analysis of the cell type-specific role of b2 integrins in vivo. To overcome this limitation, we generated a CD18 gene floxed mouse strain. Offspring generated from crossing with CD11c-Cre mice displayed efficient knockdown of b2 integrins specifically in dendritic cells (DC). Stimulated b2 integrin-deficient splenic DC showed enhanced cytokine production, and concomitantly elevated activity of signal transducers and activators of transcription (STAT) 1, 3 and 5, as well as impaired expression of suppressor of cytokine signaling (SOCS) 2-6 as assessed in bone marrow-derived (BM)DC. Paradoxically,, these BMDC also showed attenuated expression of genes involved in inflammatory signaling. In line, in experimental autoimmune encephalomyelitis mice with a conditional DC-specific b2 integrin knockdown presented with a delayed onset and milder course of disease, associated with lower frequencies of T helper cell (Th)1/Th17 in the inflamed spinal cord. Altogether, our mouse model may prove a valuable tool to study leukocyte-specific functions of b2 integrins in vivo.

2022-05-27 | GSE203448 | GEO

Expression data from murine natural killer cell subsets based on Ly49 receptor expression in C57BL/6 mice (C/I+ versus Ly49G2+ NK cells)

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

Expression data from murine natural killer cell subsets based on Ly49 receptor expression in C57BL/6 mice (C/I+ versus Ly49G2+ NK cells)

2014-09-01 | GSE56662 | GEO