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Clinical Gastroenterology and... Feb 2020
Topics: Hepatitis B virus; Humans; Patient Dropouts
PubMed: 31352094
DOI: 10.1016/j.cgh.2019.07.040 -
Clinical Gastroenterology and... Jan 2020
Topics: Alanine Transaminase; DNA, Viral; Hepatitis B e Antigens; Hepatitis B virus; Humans; Seroconversion
PubMed: 31220644
DOI: 10.1016/j.cgh.2019.06.019 -
Clinical Gastroenterology and... Aug 2020
Topics: Guanine; Hepatitis B virus; Humans
PubMed: 32684317
DOI: 10.1016/j.cgh.2020.03.024 -
Clinical Gastroenterology and... Mar 2020
Topics: Algorithms; Child; Female; Hepatitis B virus; Humans; Infectious Disease Transmission, Vertical
PubMed: 31394287
DOI: 10.1016/j.cgh.2019.07.049 -
Journal of Translational Medicine Jun 2023Acute-on-chronic liver failure (ACLF) is a severe syndrome with high short-term mortality, but the pathophysiology still remains largely unknown. Immune dysregulation...
BACKGROUND
Acute-on-chronic liver failure (ACLF) is a severe syndrome with high short-term mortality, but the pathophysiology still remains largely unknown. Immune dysregulation and metabolic disorders contribute to the progression of ACLF, but the crosstalk between immunity and metabolism during ACLF is less understood. This study aims to depict the immune microenvironment in the liver during ACLF, and explore the role of lipid metabolic disorder on immunity.
METHODS
Single-cell RNA-sequencing (scRNA-seq) was performed using the liver non-parenchymal cells (NPCs) and peripheral blood mononuclear cells (PBMCs) from healthy controls, cirrhosis patients and ACLF patients. A series of inflammation-related cytokines and chemokines were detected using liver and plasma samples. The lipid metabolomics targeted free fatty acids (FFAs) in the liver was also detected.
RESULTS
The scRNA-seq analysis of liver NPCs showed a significant increase of monocytes/macrophages (Mono/Mac) infiltration in ACLF livers, whereas the resident Kupffer cells (KCs) were exhausted. A characterized TREM2 Mono/Mac subpopulation was identified in ACLF, and showed immunosuppressive function. Combined with the scRNA-seq data from PBMCs, the pseudotime analysis revealed that the TREM2 Mono/Mac were differentiated from the peripheral monocytes and correlated with lipid metabolism-related genes including APOE, APOC1, FABP5 and TREM2. The targeted lipid metabolomics proved the accumulation of unsaturated FFAs associated with α-linolenic acid (α-LA) and α-LA metabolism and beta oxidation of very long chain fatty acids in the ACLF livers, indicating that unsaturated FFAs might promote the differentiation of TREM2 Mono/Mac during ACLF.
CONCLUSIONS
The reprogramming of macrophages was found in the liver during ACLF. The immunosuppressive TREM2 macrophages were enriched in the ACLF liver and contributed to the immunosuppressive hepatic microenvironment. The accumulation of unsaturated FFAs in the ACLF liver promoted the reprogramming of the macrophages. It might be a potential target to improve the immune deficiency of ACLF patients through regulating lipid metabolism.
Topics: Humans; Lipid Metabolism; Acute-On-Chronic Liver Failure; Hepatitis B virus; Leukocytes, Mononuclear; Macrophages; Fatty Acid-Binding Proteins
PubMed: 37380987
DOI: 10.1186/s12967-023-04294-1 -
Cellular & Molecular Immunology Jan 2022The covalently closed circular DNA (cccDNA) of HBV plays a crucial role in viral persistence and is also a risk factor for developing HBV-induced diseases, including...
The covalently closed circular DNA (cccDNA) of HBV plays a crucial role in viral persistence and is also a risk factor for developing HBV-induced diseases, including liver fibrosis. Stimulator of interferon genes (STING), a master regulator of DNA-mediated innate immune activation, is a potential therapeutic target for viral infection and virus-related diseases. In this study, agonist-induced STING signaling activation in macrophages was revealed to inhibit cccDNA-mediated transcription and HBV replication via epigenetic modification in hepatocytes. Notably, STING activation could efficiently attenuate the severity of liver injury and fibrosis in a chronic recombinant cccDNA (rcccDNA) mouse model, which is a proven suitable research platform for HBV-induced fibrosis. Mechanistically, STING-activated autophagic flux could suppress macrophage inflammasome activation, leading to the amelioration of liver injury and HBV-induced fibrosis. Overall, the activation of STING signaling could inhibit HBV replication through epigenetic suppression of cccDNA and alleviate HBV-induced liver fibrosis through the suppression of macrophage inflammasome activation by activating autophagic flux in a chronic HBV mouse model. This study suggests that targeting the STING signaling pathway may be an important therapeutic strategy to protect against persistent HBV replication and HBV-induced fibrosis.
Topics: Animals; DNA, Circular; Fibrosis; Hepatitis B virus; Liver; Mice; Signal Transduction
PubMed: 34811496
DOI: 10.1038/s41423-021-00801-w -
Zeitschrift Fur Gastroenterologie Dec 2023
Topics: Humans; Hepatitis B virus; Hepatitis D, Chronic; Gastroenterology; Hepatitis B; Hepatitis D; Metabolic Diseases; Antiviral Agents
PubMed: 38081177
DOI: 10.1055/a-2181-3162 -
Zeitschrift Fur Gastroenterologie Jul 2021
Topics: Gastroenterology; Hepatitis B; Hepatitis B virus; Humans; Metabolic Diseases
PubMed: 34255317
DOI: 10.1055/a-1498-2512 -
Hepatology (Baltimore, Md.) Aug 2019
Topics: Hepatitis B virus; Hepatocytes; Humans; Nucleotides, Cyclic
PubMed: 30991445
DOI: 10.1002/hep.30663 -
Hepatology (Baltimore, Md.) Dec 2019
Topics: Adult; Biopsy; Coinfection; Fibrosis; HIV Infections; Hepatitis B virus; Humans; Liver
PubMed: 31432525
DOI: 10.1002/hep.30901