Obesity and adverse SDoH impact NK cell function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1166336 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30826500_1.fastq.gz | Fastqsanger.gz | |||
| SRR30826500_2.fastq.gz | Fastqsanger.gz | |||
| SRR30826501_1.fastq.gz | Fastqsanger.gz | |||
| SRR30826501_2.fastq.gz | Fastqsanger.gz | |||
| SRR30826478_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:African American (AA) women are disproportionally affected by obesity, particularly in the setting of adverse social determinants of health (aSDoH), which contribute to cardiovascular disease (CVD) and cancer disparities. Obesity and aSDoH appear to impair Natural Killer cells (NKs), which are critical in the innate immune response; however, the underlying mechanisms are largely unknown. We sought to investigate signaling pathways involved in NK dysfunction related to obesity in AA women from under-resourced neighborhoods disproportionately exposed to aSDoH. We determined in freshly isolated NK cells that obesity and higher social isolation, as well as higher depression and lower socioeconomic status, are associated with a shift in NK cell subsets away from CD56dim/CD16+ cytotoxic NK cells. Using ex vivo data, we identified LDL as a serum marker related to NK cell function in an AA population from under-resourced neighborhoods. Additionally, NK cells from AA women with obesity and LDL-treated NK cells displayed a loss in NK cell function. Comparative unbiased RNA sequencing analysis revealed DUSP1-dependent signaling as a common factor. Subsequent experiments involving chemical inhibition of DUSP1 signaling and DUSP1 overexpression in NK cells highlighted the significance of DUSP1 in lysosome biogenesis and, ultimately, NK cell function. Our data demonstrate a pathway by which obesity in the setting of aSDoH may relate to NK dysfunction, making DUSP1 an important target for further investigation of CVD and cancer disparities.
2025-02-12 | GSE278321 | GEO
Project description:Natural killer (NK) cells are innate lymphocytes that play a major role in immunosurveillance against tumor initiation and metastasis spread. Signals and checkpoints that regulate NK cell fitness and function in the tumor microenvironment are not well defined. Transforming grow factor (TGF)- is a recognized suppressor of NK cells that inhibits IL-15 dependent signaling events and induces cellular transdifferentiation, however the role of other SMAD signaling pathways in NK cells is unknown. We used a global, label-free proteomics approach to compare the protein expression profiles of NK cells in the presence of TGF-b or activin-A.
2020-04-06 | PXD011672 | Pride
Project description:Obesity is linked to an increased risk of many cancers and can impair the anti-tumour immune response. This project examined the effect of different sources of dietary fats on tumour immunity using a syngeneic model of melanoma in mice fed high fat diets (HFD) derived from different sources. HFD based on beef tallow, lard and butter increased tumour growth in this model, while HFD derived from coconut oil, palm oil or olive oil did not. Further experiments focusing on butter and palm oil based HFD found differential regulation of natural killer (NK) cells and CD8 T-cell infiltration and function in the tumour microenvironment, and identified enrichment in immunosuppressive long chain acylcarnitine species in mice fed a HFD based on butter compared to palm oil. This dataset contains proteomic data from NK cells from mice fed a standard fat diet (SFD), NK cells from mice fed a HFD based on butter and from mice fed a HFD based on palm oil.
2025-06-03 | PXD062745 | Pride
Project description:Dengue is a mosquito-borne virus infection affecting half of the world’s population for which therapies are lacking. The role of T and NK-cells in protection/immunopathogenesis remains unclear for dengue for dengue. We performed a longitudinal phenotypic, functional and transcriptional analyses of T and NK-cells in 124 dengue patients using flow cytometry and single-cell RNA-sequencing. We show that T/NK-cell signatures early in infection discriminate patients who will progressdevelop to severe dengue (SD) from those who do not. These signatures are exacerbated in In patients with overweight/obesity these signatures are exacerbated compared to healthy weight patients, supporting their increased susceptibility to SD. In SD, CD4+/CD8+ T-cells and NK-cells display increased co-inhibitory receptor expression and decreased cytotoxic capacity potential compared to non-SD. Using transcriptional and proteomics approaches we demonstrate decreased Furthermore, type-I Interferon signalling is downregulatedresponses in SD, suggesting defective innate immunity virus-sensing mechanisms may underlie NK/T-cell dysfunction.
2025-05-21 | PXD061694 | Pride
Project description:The surface receptor CD8a is present on 20-80% of human (but not mouse) NK cells, yet its function on NK cells remains poorly understood. CD8a expression on donor NK cells was associated with a lack of therapeutic responses for leukemia patients in prior studies, thus we hypothesized that CD8a may impact critical NK cell functions. Here, we discovered that CD8a- NK cells had improved control of leukemia in xenograft models, compared to CD8a+ NK cells, likely due to an enhanced capacity for proliferation. Unexpectedly, CD8a expression was induced on approximately 30% of previously CD8a- NK cells following IL-15 stimulation. These ‘induced’ CD8a+ (‘iCD8a+’) NK cells had the greatest proliferation, responses to IL-15 signaling, and metabolic activity, compared to those that sustained existing CD8a expression (‘sustained CD8a+) or those that remained CD8a- (‘persistent CD8a-‘). These iCD8a+ cells originated from an IL-15Rb high NK cell population, with CD8a expression dependent on the transcription factor RUNX3. Moreover, CD8A CRISPR/Cas9 deletion resulted in enhanced responses through the activating receptor NKp30, possibly by modulating KIR inhibitory function. Thus, CD8a status identifies human NK cell capacity for IL-15-induced proliferation and metabolism in a time-dependent fashion and exhibits a suppressive effect on NK cell activating receptors
2024-06-20 | GSE263686 | GEO
Project description:An intrinsic property of the heart is an ability to rapidly and coordinately adjust flux through metabolic pathways in response to physiologic stimuli (termed metabolic flexibility). Cardiac metabolism also fluctuates across the 24-hr day, in association with diurnal sleep-wake and fasting-feeding cycles. Although loss of metabolic flexibility has been proposed to play a causal role in the pathogenesis of cardiac disease, it is currently unknown whether day-night variations in cardiac metabolism are altered during disease states. Here, we tested the hypothesis that diet-induced obesity disrupts cardiac “diurnal metabolic flexibility”, which is normalized by time-of-day-restricted feeding. Chronic high fat feeding (20-wk) induced obesity in mice, abolished diurnal rhythms in whole body metabolic flexibility, and increased markers of adverse cardiac remodeling (hypertrophy, fibrosis, and steatosis). RNAseq analysis revealed that 24-hr rhythms in the cardiac transcriptome were dramatically altered during obesity; only 22% of rhythmic transcripts in control hearts were unaffected by obesity. However, day-night differences in cardiac substrate oxidation were essentially identical in control and high fat fed mice. In contrast, day-night differences in both cardiac triglyceride synthesis and lipidome were abolished during obesity. Next, a subset of obese mice (induced by 18-wks ad libitum high fat feeding) were allowed access to the high fat diet only during the 12-hr dark (active) phase, for a 2-wk period. Dark phase restricted feeding partially restored whole body metabolic flexibility, as well as day-night differences in cardiac triglyceride synthesis and lipidome. Moreover, this intervention partially reversed adverse cardiac remodeling in obese mice. Collectively, these studies reveal diurnal metabolic inflexibility of the heart during obesity specifically for non-oxidative lipid metabolism (but not for substrate oxidation), and that restricting food intake to the active period partially reverses obesity-induced cardiac lipid metabolism abnormalities and adverse remodeling of the heart.
2021-04-09 | GSE171710 | GEO
Project description:T cell impact rituximab-mediated NK cell transcriptomics
| PRJNA688891 | ENA
Project description:NK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent. To identify Runx3 responsive genes, NK cells were isolated from spleen of WT and Runx3-/- mice . Six samples (3 WT and 3 Runx3-/-) of freshly isolated NK cells (resting) were separately obtained from individual mice.
2013-11-18 | E-GEOD-50123 | biostudies-arrayexpress
Project description:Somatic STAT5B gain-of-function mutations have been frequently found in patients with T- and NK-cell neoplasms. STAT5BN642H represents the most frequently occuring STAT5B mutation. To investigate the molecular mechanism of STAT5BN642H-driven NK-cell leukemia, we performed RNA-Seq of liver derived FACS-sorted diseased N642HNK/NK and aged non-diseased control (Cre neg, GFPNK/NK), STAT5BNK/NK, N642HNK/NK NK cells.
2024-05-01 | E-MTAB-13797 | biostudies-arrayexpress
Project description:Semaglutide attenuates obesity-induced impact on intestinal epithelium
| PRJNA1085697 | ENA