Peritoneal macrophage heterogeneity in decompensated liver cirrhosis
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ABSTRACT:
PROVIDER: PRJNA514059 | ENA |
REPOSITORIES: ENA
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Project description:Peritoneal macrophages (PM) are thought to regulate peritoneal inflammation and control bacterial infections in decompensated liver cirrhosis. The aim of this study was to characterize human PM heterogeneity. Employing CD206 surface expression, we identified subsets of human large (LPM) and small (SPM) PM, which differed in granularity and maturation states. FACS-sorted LPM from patients with decompensated cirrhosis revealed discrete transcriptome clusters, comprising more than 4000 differentially regulated genes involved in cell cycle, metabolism, and immune signaling.
2020-03-24 | GSE124878 | GEO
Project description:Objectives Non-invasive staging of decompensated cirrhosis is an unmeet clinical need. The aims of this study were to characterize and validate a novel miRNA signature to stage decompensated cirrhosis and predict the portal pressure and cardiac dysfunction response to non-selective beta-blockers (NSBB). Design Serum samples from patients with decompensated cirrhosis (n=36) and healthy controls (n=36) were tested for a novel signature of five miRNAs (miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p) identified in the secretome of primary human hepatocytes, and three miRNAs (miR-192-5p, miR-34a-5p and miR-29a-5p) previously discovered as biomarkers of chronic liver disease. All patients had ascites, that was refractory in 18 (50%), and were placed on NSBB for variceal bleeding prophylaxis. In all patients, serum miRNAs, hepatic venous pressure gradient (HVPG), and echocardiogram study was performed before and 1 month after NSBB. Results Cirrhotic patients had lower serum levels of miR-429, miR-885-5p, miR-181b-5p, miR-122-5p, miR-192-5p and miR-29a-5p (p<0.05). miR-452-5p and miR-429 expression were lower in NSBB responders (p=0.006). miR-181b-5p expression was greater in refractory- than in diuretic sensitive ascites (p=0.008) and correlated with serum creatinine. miR-452-5p and miR-885-5p were inversely correlated with baseline systemic vascular resistance (ρ=-0.46 p=0.007; and ρ=-0.41 p=0.01 respectively), and with diminished systolic contractility in patients with refractory ascites after NSBB (ρ=-0.55 p=0.02; and ρ=-0.55 p=0.02, respectively). Conclusion Analysis of a miRNA signature in serum distinguishes patients with decompensated cirrhosis who show more severe systemic circulatory dysfunction and compromised systolic function after beta-blockade, and those more likely to benefit from NSBB.
2021-02-10 | GSE150867 | GEO
Project description:Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesising that innate immune dysfunction contributes to susceptibility to infection, we assessed ascitic fluid macrophage phenotype and function. The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage sub-populations. The proportion of CRIgHi macrophages differed between patients, and in the same patient over time, and a high proportion of CRIgHi macrophages was associated with reduced disease severity (Model for End Stage Liver Disease (MELD)) score. As compared to CRIgLow macrophages, CRIgHi macrophages were highly phagocytic and displayed enhanced antimicrobial effector activity. Transcriptional profiling by RNA Sequencing and comparison with human macrophage and murine peritoneal macrophage expression signatures highlighted similarities between CRIgHi cells, human macrophages and mouse F4/80Hi resident peritoneal macrophages, and between CRIgLow macrophages, human monocytes and mouse F4/80Low monocyte-derived peritoneal macrophages. These data suggest CRIgHi and CRIgLow macrophages may represent a tissue-resident population and a monocyte-derived population, respectively. In conclusion, ascites fluid macrophage subset distribution and phagocytic capacity is highly variable between patients with chronic liver disease. Regulating the numbers and/or functions of these macrophage populations could provide therapeutic opportunities in cirrhotic patients.
2017-08-22 | GSE79833 | GEO
Project description:BACKGROUND AND AIMS: The effects of intravenous albumin on lymphocyte perturbations and defective neutrophil anti-microbial functions that characterize patients with acute-on-chronic liver failure (ACLF) are unknown. METHODS: Forty-nine patients admitted for severe acutely decompensated cirrhosis without ACLF were investigated with the use of whole-blood RNA sequencing (RNA-seq) on admission and after a median period of 15 days once they had developed ACLF. Such patients were selected because they follow a steady systemic inflammation course. Thirty patients had received albumin during the progression to ACLF but not the 19 others. Single-cell RNA-seq (scRNA-seq) in peripheral blood mononuclear cells (PBMCs) exposed ex vivo to albumin or vehicle for 2 hours, and assessment of the anti-microbial capacity of neutrophils exposed ex vivo to albumin were performed in additional patients with acutely decompensated cirrhosis. RESULTS: Analysis of whole-blood RNA-seq data revealed that patients who had received albumin exhibited specific upregulation of signatures related to B cells, plasma cells and immunoglobulins; CD4 T cells; myeloid cells; mismatch repair, cell cycle and mitosis; and transcription factors such as c-Myc and E2F family members. The use of scRNA-seq to analyze patients' PBMCs exposed ex vivo to albumin showed increases in signatures related to B cells, myeloid cells, and CD4 T cells. Neutrophils exposed ex vivo to albumin exhibited increased chemotactic and degranulation responses, enhanced phagocytosis, and increased pathogen-destroying swarming functions. CONCLUSIONS: In patients with severe acutely decompensated cirrhosis, albumin rewires transcription in B cells, CD4 T cells and mononuclear myeloid cells, and resets neutrophil anti-microbial functions to normal.
2025-04-08 | GSE171741 | GEO
Project description:MOLECULAR PROFILING OF DECOMPENSATED CIRRHOSIS BY A NOVEL microRNA SIGNATURE
| PRJNA633887 | ENA
Project description:Transcriptome analysis of two population of peritoneal mononuclear phagocytes (CD14+ macrophages and CD1c+ dendritic cells) in peritoneal dialysis effluent from stable (infection-free) peritoneal dialysis patients.
2017-01-23 | E-MTAB-5439 | biostudies-arrayexpress
Project description:Bone marrow derived macrophage vs peritoneal macrophage
| PRJNA414129 | ENA
Project description:In this study, we profiled the precision N-glycoproteome of the murine peritoneal macrophage under different stimulation.
2021-06-12 | PXD026629 | Pride
Project description:Albumin treatment transcriptionally reprograms circulating immune cells in patients with acutely decompensated cirrhosis
| PRJNA720693 | ENA
Project description:Immunometabolism is a rapidly growing field, which has led to greater understanding of innate immune cell functions. Macrophages are at the core of this research: polarized subsets of in vitro-derived cells reportedly utilize select metabolic pathways to maintain their phenotype. However, relevance of these in vitro studies to the in vivo setting is not known, and metabolic requirements are likely dependent on unique physiological and cellular metabolic environments. Here we define the metabolic requirements of peritoneal tissue-resident macrophages, the accessibility of these metabolites to cells in the peritoneum, and we dissect the role of this unique environment in maintaining a crucial macrophage function. We find that the peritoneal cavity is enriched in amino acids, most notably glutamate. Peritoneal tissue-resident macrophages have an extraordinarily large mitochondrial capacity compared with other phagocytes; this is primarily fueled by glutaminolysis, which is additionally required to maintain an extensive respiratory burst. Glutaminolysis fuels the electron transport chain, which is enhanced during tissue-resident macrophage respiratory burst via a switch to dependence of mitochondrial complex-II. This is not dependent on the level of NADPH, but requires p47 maintained NADPH-oxidase activity. Therefore, we propose that tissue-resident macrophages exploit their unique metabolic niche by implementing their glutamine-fueled mitochondrial-rich phenotype to sustain respiratory burst to assault pathogens, showing that cell-specific metabolic underpinning is important for function. Importantly, we also find that glutamine is required for the respiratory burst in human monocytes, which highlights that metabolites are not species-specific and can be the link between cellular mechanism in mouse and man.
2017-10-13 | GSE104920 | GEO