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Series GSE93265 Query DataSets for GSE93265
Status Public on Feb 06, 2019
Title Human monocytes exhibit a functional and transcriptional reprogramming during Acute-on-Chronic-Liver-Failure with a key role for IL-10
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Background and aims: Acute-on-chronic liver failure (ACLF) is characterized by rapid deterioration of liver function and organ failure, whereby immunoparesis and susceptibility to infections often precipitate this syndrome. Here we characterized the events triggering immune dysfunction in monocytes within alcoholic liver disease. Methods: We evaluated the frequency of monocyte subsets, their intracellular IL10 production, surface HLA-DR expression, and phagocytic and oxidative burst capacity in patients with decompensated cirrhosis, -alcoholic hepatitis or ACLF. RNAsequencing of ACLF patient-derived CD14+ monocytes were performed either immediately or after 12-hour culture in the presence or absence of plasma from ACLF patients. In this in vitro model of ACLF induction in CD14+ monocytes we characterized the early molecular, immunological and functional changes. Results: Besides a redistribution of monocyte subset composition, ACLF patient-derived monocytes featured elevated frequencies of IL-10-producing cells, reduced HLA-DR expression and impaired phagocytic- and oxidative burst capacity. RNAsequencing revealed a reprogramming of ACLF monocytes, whereby they undergo a transition from a pro-inflammatory to an immunosuppressive- and altered metabolic status. Culturing healthy monocytes in the presence of ACLF plasma, blunted their phagocytic capacity and triggered a gene expression pattern comparable to ACLF patients. Conversely, culturing patient monocytes in normal plasma restored their phagocytic capacity.  Finally, plasma IL-10 levels correlated with patient survival. Conclusion: ACLF monocytes featured a defective immunosuppressive and -glycolytic profile, an attribute which could be mimicked by culturing healthy monocytes in the presence of ACLF patient plasma. Our data implicate a role for IL-10 signaling pathways in triggering monocytes dysfunction and opens up new avenues for therapeutic targeting.
 
Overall design The study included 27 samples, RNA from purified CD14+ monocytes. 5 samples were from ACLF patients (cells immediately after isolation), 4 samples from healthy human controls immediately after isolation, 5 ACLF patients in vitro cultured in the presence of pool of ACLF serum, 5 ACLF patients in vitro cultured in the presence of pool of normal human serum, 4 healthy controls in vitro cultured in the presence of pool of ACLF serum, 4 healthy controls in vitro cultured in the presence of pool of normal human serum.
 
Contributor(s) Korf H, du Plessis J, van der Merwe S, van Pelt J
Citation(s) 30580251
Submission date Jan 06, 2017
Last update date May 15, 2019
Contact name Rekin's Janky
E-mail(s) Nucleomics.Bioinformatics@vib.be
Organization name VIB
Department Nucleomics Core
Street address Herestraat 49 Box 816
City Leuven
ZIP/Postal code B-3000
Country Belgium
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (27)
GSM2449421 Control1-T0
GSM2449422 Control1-T1-ACLF
GSM2449423 Control1-T1-Normal
Relations
BioProject PRJNA360435
SRA SRP096201

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Supplementary file Size Download File type/resource
GSE93265_RawCounts.xlsx.gz 4.5 Mb (ftp)(http) XLSX
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Processed data are available on Series record
Raw data are available in SRA

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