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Series GSE135284 Query DataSets for GSE135284
Status Public on Aug 02, 2020
Title Epigenetic basis for monocyte dysfunction in acute-on-chronic liver failure and alcoholic hepatitis [ATAC-seq]
Organism Homo sapiens
Experiment type Other
Severe forms of alcoholic liver disease are associated with increased susceptibility to infections largely due to immune dysfunction. In this study, we analyze the phenotypic, molecular and functional profiles of the mononuclear phagocyte system of patients with cirrhosis, severe alcoholic hepatitis (sAH) or acute-on-chronic liver failure (ACLF).
RESULTS: sAH and ACLF patients display a severe impairment of the TH1-promoting IL-12p70/IFNgamma/CXCL10 axis. Furthermore, the CD14+ monocytes and classical dendritic cells of these patients are unable to mount an appropriate pro-inflammatory response after stimulation with PAMPs associated with gram-negative bacteria or fungal pathogens. These cells also have reduced polyfunctionality, which is associated with a higher risk of subsequent infection. Finally, we show that CD14+ monocytes of sAH and ACLF patients display a similar transcriptional profile characterized by immunosuppressive features. This was accompanied with changes in chromatin accessibility in enhancer regions of key immune and metabolic genes.
CONCLUSIONS: Altered transcriptional program and functional properties of monocytes from sAH and ACLF patients has strong epigenetic determinants.
Overall design We recruited 39 patients with alcoholic cirrhosis (including 11 patients with sAH and 12 with ACLF), 12 healthy controls and 11 patients with chronic alcohol consumption. We performed whole blood phenotypic analysis of surface markers and stimulation with various pathogen-associated molecular patterns (PAMPs). We also performed RNAseq and ATACseq on CD14+ monocytes from 6 HC, 4 sHA and 4 ACLF patients.
Contributor(s) Weichselbaum L, Azouz A, Smolen KK, Das J, Splittgerber M, Libert F, Gustot T, Goriely S
Citation(s) 32145259
Submission date Aug 02, 2019
Last update date Nov 02, 2020
Contact name Stanislas Goriely
Phone +3226509586
Organization name Université Libre de Bruxelles
Street address Rue Adrienne Bolland 8
City Gosselies
ZIP/Postal code B-6041
Country Belgium
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (15)
GSM4002719 ATAC_HC38
GSM4002720 ATAC_HC40
GSM4002721 ATAC_HC47
This SubSeries is part of SuperSeries:
GSE135286 Epigenetic basis for monocyte dysfunction in acute-on-chronic liver failure and alcoholic hepatitis
BioProject PRJNA558249
SRA SRP217123

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Supplementary file Size Download File type/resource
GSE135284_RAW.tar 1.6 Gb (http)(custom) TAR (of BIGWIG, NARROWPEAK)
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Raw data are available in SRA
Processed data provided as supplementary file

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