Immunometabolic adaptation in monocytes underpins functional changes during pregnancy. [MYELOID]
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ABSTRACT:
PROVIDER: PRJNA1074330 | ENA |
REPOSITORIES: ENA
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Project description:Immunometabolic adaptation in monocytes underpins functional changes during pregnancy [metabolism]
| PRJNA1074320 | ENA
Project description:Metabolic heterogeneity is a determinant of immune cell function. The normal physiological metabolic reprogramming of pregnancy that ensures the fuel requirements of mother and baby are met might also underpin changes in innate and adaptive immunity that occur with pregnancy and manifest as altered responses to pathogens and changes to autoimmune disease symptoms. Here, we use peripheral blood monocytes, susceptible to microenvironmentally determined reprogramming of metabolism, to determine if pregnancy at term provokes an altered metabolic profile that underpins functional change. Focusing on late gestation where any effect will be most profound, we reveal that monocytes lose M2-like and gain M1-like properties accompanied by reductions in mitochondrial mass, maximal respiration and cardiolipin content in pregnancy; glycolysis is unperturbed. We establish that muramyl dipeptide (MDP)-stimulated cytokine production relies on oxidative metabolism then show that reduced monocyte oxidative metabolism with pregnancy compromises the production of TNF and IL-6 in response to MDP but not LPS. Overall, mitochondrially centred metabolic capabilities of late gestation monocytes are downregulated revealing natural plasticity in monocyte phenotype and function that could reveal targets for improving pregnancy outcomes but also yield new therapeutic approaches to diverse metabolic and/or immune-mediated diseases beyond pregnancy.
2024-04-26 | PXD050094 | Pride
Project description:Metabolic heterogeneity is a determinant of immune cell function. The normal physiological metabolic reprogramming of pregnancy that ensures the fuel requirements of mother and baby are met might also underpin changes in innate and adaptive immunity that occur with pregnancy and manifest as altered responses to pathogens and changes to autoimmune disease symptoms. Here, we use peripheral blood monocytes, susceptible to microenvironmentally determined reprogramming of metabolism, to determine if pregnancy at term provokes an altered metabolic profile that underpins functional change. Focusing on late gestation where any effect will be most profound, we reveal that monocytes lose M2-like and gain M1-like properties accompanied by reductions in mitochondrial mass, maximal respiration and cardiolipin content in pregnancy; glycolysis is unperturbed. We establish that muramyl dipeptide (MDP)-stimulated cytokine production relies on oxidative metabolism then show that reduced monocyte oxidative metabolism with pregnancy compromises the production of TNF and IL-6 in response to MDP but not LPS. Overall, mitochondrially centred metabolic capabilities of late gestation monocytes are downregulated revealing natural plasticity in monocyte phenotype and function that could reveal targets for improving pregnancy outcomes but also yield new therapeutic approaches to diverse metabolic and/or immune-mediated diseases beyond pregnancy.
2024-04-01 | GSE255271 | GEO
Project description:Metabolic heterogeneity is a determinant of immune cell function. The normal physiological metabolic reprogramming of pregnancy that ensures the fuel requirements of mother and baby are met might also underpin changes in innate and adaptive immunity that occur with pregnancy and manifest as altered responses to pathogens and changes to autoimmune disease symptoms. Here, we use peripheral blood monocytes, susceptible to microenvironmentally determined reprogramming of metabolism, to determine if pregnancy at term provokes an altered metabolic profile that underpins functional change. Focusing on late gestation where any effect will be most profound, we reveal that monocytes lose M2-like and gain M1-like properties accompanied by reductions in mitochondrial mass, maximal respiration and cardiolipin content in pregnancy; glycolysis is unperturbed. We establish that muramyl dipeptide (MDP)-stimulated cytokine production relies on oxidative metabolism then show that reduced monocyte oxidative metabolism with pregnancy compromises the production of TNF and IL-6 in response to MDP but not LPS. Overall, mitochondrially centred metabolic capabilities of late gestation monocytes are downregulated revealing natural plasticity in monocyte phenotype and function that could reveal targets for improving pregnancy outcomes but also yield new therapeutic approaches to diverse metabolic and/or immune-mediated diseases beyond pregnancy.
2024-04-01 | GSE255273 | GEO
Project description:Ezrin, an actin-binding protein, plays a crucial role in organizing the cellular cortical cytoskeleton and plasma membrane during cell migration, adhesion, and proliferation. While there is a good understanding of ezrin's function in cell types such as epithelial cells and lymphocytes, its role in monocytes/macrophages (MΦs) is less understood. Here, we used a monocyte/MΦ-specific ezrin knock-out mouse model to investigate the contribution of ezrin to monocyte recruitment and adaptation to the lung extracellular matrix (ECM) in response to lipopolysaccharide (LPS). Our study revealed that LPS induces ezrin expression in monocytes/MΦs, and that ezrin is essential for monocytes to adhere to lung ECM, proliferate, and differentiate into tissue-resident interstitial MΦs. Notably, ezrin is not required for monocyte extravasation into the lung parenchyma. Mechanistically, the loss of ezrin in monocytes disrupts activation of FAK and AKT signaling, which are necessary for lung-recruited monocytes and monocyte-derived MΦs to adhere to the ECM, proliferate, and survive. In summary, our data suggest that ezrin plays a role beyond structural cellular support, influencing diverse monocytes/MΦ processes and signaling pathways in response to infections, driving their adaptation to the lung microenvironment.
2024-11-07 | GSE267506 | GEO
Project description:A disrupted FOXP3 transcriptional signature underpins regulatory T cells insufficiency in early pregnancy failure
| PRJNA1001301 | ENA
Project description:Ezrin drives adaptation of monocytes to the inflamed lung microenvironment
| PRJNA1111746 | ENA
Project description:The human uterus undergoes profound physiological tissue remodelling during pregnancy. In the myometrium, altered gene expression must underlie these extensive molecular and structural changes. The purpose of this study was to compare expression profiles of pregnant and non-pregnant myometrium, in order to identify genes that participate in this process. mRNA from 14 non-pregnant and four pregnant human myometrial samples were analysed using a human UniGEM V microarray with 7075 cDNA elements. A total of 602 transcripts from the microarray were up-regulated >=2.0-fold in pregnant myometrium, with 37 transcripts up-regulated >=4.0-fold. In contrast, eight transcripts were down-regulated >=2.0-fold in pregnancy. To ensure accurate representation of differential gene expression, Northern blot analyses using total RNA from 16 samples of non-pregnant and pregnant myometrium were used to examine mRNA levels for four of the genes that were differentially expressed by microarray analysis, namely plasminogen activator inhibitor type 1 (PAI-1), milk fat globule-EGF factor 8 protein (MFGE8), secreted frizzled-related protein 4 (sFRP4) and estrogen receptor {alpha} (ER{alpha}). On the microarray these transcripts were up-regulated 7.5-fold for PAI-1 and 4.9-fold for MFGE8 in pregnant myometrium, and down-regulated 3.7-fold for sFRP4 and 2.9-fold for ER{alpha} in pregnancy. Northern blot analyses confirmed these changes. Our findings suggest that microarray technology is a useful tool for examining global changes in gene expression that occur as the myometrium differentiates from non-pregnant to pregnant status. Defining these changes provides new insight into the structural and functional adaptations of human myometrium during pregnancy. Keywords: other
2005-07-18 | GSE2957 | GEO
Project description:The aim of our work was to evaluate what happens to the two most polar subpopulations of peripheral blood monocytes in women diagnosed preeclampsia in comparison with physiological pregnancy. We used microarrays for comparison of CD14+ and CD16+ monocytes from patients with preeclampsia and women with physiological pregnancy
2021-10-31 | GSE186819 | GEO
Project description:NRF2 deficiency leads to inadequate beta cell adaptation during pregnancy and gestational diabetes
| PRJNA1221270 | ENA