Immune suppression in chronic hepatitis B infection associated liver disease: A review

Li, Tianyang; Yang, Yang; Zhou, Guo; Tu, Zhengkun

doi:10.3748/wjg.v25.i27.3527

Cited by 119 publications

(129 citation statements)

References 105 publications

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“…Abnormal metabolism widely influences the development of liver damage. Although HBV has been described as a typical non-cytopathic virus, it can induce tissue damage of variable severity by stimulating a protective immune response, that can simultaneously cause damage and protection 11 .…”

Section: Introductionmentioning

confidence: 99%

Chronic ethanol consumption and HBV induce abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activate Tregs in HBV-Tg mice

et al. 2020

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Rationale: Chronic ethanol consumption as a public health problem worldwide boosts the development of chronic liver diseases in hepatitis B virus (HBV)-infected patients. Arachidonic acid metabolite prostaglandin E2 (PGE2) activates regulatory T cells (Tregs) function. Here, we aim to investigate the underlying mechanism by which chronic ethanol consumption enriches the HBV-induced abnormal lipid metabolism and Tregs. Methods: The si-RNAs were used to weaken the expression of SWELL1 in HepG2, HepG2.2.15 and K180 cancer cell lines, followed by RNA sequencing from HepG2 cells. Arachidonic acid metabolite PGE2 and LTD4 were measured by ELISA assay in vivo and in vitro. Western blot analysis and RT-qPCR were used to examine HBx and SWELL1 and transcriptional factor Sp1 in clinical HCC samples and cell lines. The effect of chronic ethanol consumption on Tregs was tested by flow cytometry in HBV-Tg mice. The splenic Tregs were collected and analyzed by RNA sequencing. Results: The cooperative effect of ethanol and HBV in abnormal lipid metabolism was observed in vivo and in vitro . The depression of SWELL1 (or HBx) resulted in the reduction of lipid content and arachidonic acid metabolite, correlating with suppression of relative gene atlas. Ethanol and SWELL1 elevated the levels of PGE2 or LTD4 in the liver of mice and cell lines. Interestingly, the ethanol modulated abnormal lipid metabolism through activating HBx/Sp1/SWELL1/arachidonic acid signaling. Chronic ethanol consumption remarkably increased the population of PBL Tregs and splenic Tregs in HBV-Tg mice, consistently with the enhanced expression of PD-L1 in vivo and in vitro . Mechanically, RNA-seq data showed that multiple genes were altered in the transcriptomic atlas of Tregs sorting from ethanol-fed mice or HBV-Tg mice. Conclusion: The chronic ethanol intake enriches the HBV-enhanced abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activates Tregs in mice.

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Section: Introductionmentioning

confidence: 99%

Chronic ethanol consumption and HBV induce abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activate Tregs in HBV-Tg mice

et al. 2020

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“…HCC is the leading cause of cancer-related morbidity and mortality worldwide, and most incidences are associated with cirrhosis related to chronic hepatitis virus infection (15). Currently, it is believed that immune escape contributes to the development of HCC caused by viral hepatitis infection-particularly hepatitis B virus (16). The liver is a key immune organ that plays a protective role by promoting immune tolerance.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Study of Tumor Immune Microenvironment and Relevant Genes in Hepatocellular Carcinoma Identifies Potential Prognostic Significance

Chen

Zhang

et al. 2020

Front. Oncol.

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Background: The tumor immune microenvironment (TIME) is an external immune system that regulates tumorigenesis. However, cellular interactions involving the TIME in hepatocellular carcinoma (HCC) are poorly characterized. Methods: In this study, we used multidimensional bioinformatic methods to comprehensively analyze cellular TIME characteristics in 735 HCC patients. Additionally, we explored associations involving TIME molecular subtypes and gene types and clinicopathological features to construct a prognostic signature. Results: Based on their characteristics, we classified TIME and gene signatures into three phenotypes (TIME T1-3) and two gene clusters (Gene G1-2), respectively. Further analysis revealed that Gene G1 was associated with immune activation and surveillance and included CD8 + T cells, natural killer cell activation, and activated CD4 + memory T cells. In contrast, Gene G2 was characterized by increased M0 macrophage and regulatory T cell levels. After calculation of principal component algorithms, a TIME score (TS) model, including 78 differentially expressed genes, was constructed based on TIME phenotypes and gene clusters. Furthermore, we observed that the Gene G2 cluster was characterized by high TS, and Gene G1 was characterized by low TS, which correlated with poor and favorable prognosis of HCC, respectively. Correlation analysis showed that TS had a positive association with several clinicopathologic signatures [such as grade, stage, tumor (T), and node (N)] and known somatic gene mutations (such as TP53 and CTNNB1). The prognostic value of the TS model was verified using external data sets. Conclusion: We constructed a TS model based on differentially expressed genes and involving immune phenotypes and demonstrated that the TS model is an effective prognostic biomarker and predictor for HCC patients.

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“…[ 42 ] In CHB patients, elevated IL-10 production was perceived to cause impaired secretion of IFN-γ by NK cells but without altering cytotoxicity. [ 43 – 45 ] IL-10 production was significantly reduced in subjects with HIV/HBV-coinfection than in subjects infected with HBV alone. Another major finding of this study was that IFN-γ production levels are higher and CD107a expression is stronger in subjects with HIV/HBV-coinfection than in subjects infected with HBV alone.…”

Section: Discussionmentioning

confidence: 98%

NKG2C+ natural killer cell function improves the control of HBV replication in individuals with acute HIV infection coinfected with HBV

Song

et al. 2020

Medicine

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Individuals infected with hepatitis B virus (HBV) are often coinfected with human immunodeficiency virus (HIV). However, individuals with chronic HBV infection living with acute HIV infection have a significantly lower HBV viral load, along with higher HBeAg and HBsAg loss than HBV-infected individuals alone. Here, we investigated the possible role of natural killer cells (NK cell) function in this progressive course to explore the relationship between phenotypic/functional changes in NK cells during acute HIV infection and HBV clearance in patients with HIV/HBV coinfection. Peripheral blood NK cells from 38 patients with primary HIV infection, including 20 with untreated HIV infection and 18 treatment-naïve patients with HIV/HBV coinfection and 16 patients with chronic HBV infection, were enrolled in this study. We found that the HIV/HBV-coinfected individuals had higher levels of NK cells than the HBV-infected individuals, due to expansion of the CD56 neg NK cell population. The proportion of NK cells in CD56 dim and CD56 bri NK subsets was not found significant difference between HIV/HBV-coinfected and HBV-infected individuals. However, NKG2C levels on NK cells and subsets were significantly higher in HIV/HBV-coinfected individuals than in HBV-infected individuals, whereas NKG2A levels were unaffected or decreased. In addition, the levels of degranulation CD107a, cytotoxicity and IFN-γ production of NK cells were increased in HIV/HBV-coinfected individuals than in HBV-infected individuals. The level of IL-10 production of NK cells was decreased in HIV/HBV-coinfected individuals than in HBV-infected individuals. Furthermore, the level of HBV-DNA was inversely correlated with the proportion of NKG2C + and NKG2C + NKG2A − NK cells, while positively correlated with the proportion of NKG2A + and NKG2C - NKG2A + NK cells. IFN-γ production was inversely correlated with levels of HBV-DNA, but the CD107a expression and IL-10 production of NK cells were not correlated with HBV-DNA levels. These results demonstrate that the upregulation of NKG2C expression, but not of NKG2A expression on the surface of NK cells increases cytolytic capacity and the amounts of cytokines produced and may play a crucial role in HBV clearance during HIV/HBV-coinfection.

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Immune suppression in chronic hepatitis B infection associated liver disease: A review

Cited by 119 publications

References 105 publications

Chronic ethanol consumption and HBV induce abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activate Tregs in HBV-Tg mice

Chronic ethanol consumption and HBV induce abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activate Tregs in HBV-Tg mice

Comprehensive Study of Tumor Immune Microenvironment and Relevant Genes in Hepatocellular Carcinoma Identifies Potential Prognostic Significance

NKG2C+ natural killer cell function improves the control of HBV replication in individuals with acute HIV infection coinfected with HBV

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