Chronic ethanol diet increases regulatory <scp>T</scp>‐cell activity and inhibits hepatitis <scp>C</scp> virus core‐specific cellular immune responses in mice

Ortiz, Vivian; Wands, Jack R.

doi:10.1111/hepr.12173

Cited by 11 publications

(9 citation statements)

References 48 publications

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“…Clinical studies also indicate that alcohol consumption is associated with increases in HCV replication and disease progression [43, 44], which is similar to the delayed viral clearance observed in our mouse model (Fig. 2) as well as to recently published work [16, 45]. …”

Section: Discussionsupporting

confidence: 90%

Alcohol intake alters immune responses and promotes CNS viral persistence in mice

Loftis

Taylor

Raué

et al. 2016

Behavioural Brain Research

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Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n = 94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60 days post-infection and continued to receive 24-hour access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8+ T cell frequencies (particularly CD11ahi subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection.

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Section: Discussionsupporting

confidence: 90%

Alcohol intake alters immune responses and promotes CNS viral persistence in mice

Loftis

Taylor

Raué

et al. 2016

Behavioural Brain Research

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“…It has been reported that the ethanol-caused elevated-Tregs are of great significance 39 . However, the effect of ethanol on Tregs is not well documented when the liver is infected by HBV.…”

Section: Resultsmentioning

confidence: 99%

“…A great portion of CHB patients are suffering from concomitant ALD, which is a public health problem worldwide. It has been reported that chronic ethanol consumption disrupts cholesterol homeostasis 10 , and ethanol-caused elevated-Tregs are of great significance 39 . However, the significance of ethanol in the moudulation of HBV-induced abnormal lipid and Tregs is elusive.…”

Section: Discussionmentioning

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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“…Moreover, Treg population is likely to be involved in the mechanism of hepatitis viral infection in alcoholics. Increased CD25 + FOXP3 + and CD4 + FOXP3 + Treg populations induced by immunization with HCV core-containing DCs from ethanol-fed mice might be responsible for the suppression of HCV core-specific CD4 + and CD8 + T-cell immune responses (104). IL-17-producing T helper 17 (T H 17) effector cells, a subset of T helper cells distinct from T H 1 and T H 2 CD4 + T cells, were identified in the circulation and livers of patients with ALD (105).…”

Section: Adaptive Immune Cellsmentioning

confidence: 99%

Recent Insights Into the Role of Immune Cells in Alcoholic Liver Disease

Tan

Wang

et al. 2019

Front. Immunol.

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Accumulating clinical and experimental evidences have demonstrated that both innate and adaptive immunity are involved in the pathogenesis of alcoholic liver disease (ALD), in which the role of immunity is to fuel the inflammation and to drive the progression of ALD. Various immune cells are implicated in the pathogenesis of ALD. The activation of innate immune cells induced by alcohol and adaptive immune response triggered by oxidative modification of hepatic constituents facilitate the persistent hepatic inflammation. Meanwhile, the suppressed antigen-presenting capability of various innate immune cells and impaired function of T cells may consequently lead to an increased risk of infection in the patients with advanced ALD. In this review, we summarized the significant recent findings of immune cells participating in ALD. The pathways and molecules involved in the regulation of specific immune cells, and novel mediators protecting the liver from alcoholic injury via affecting these cells are particularly highlighted. This review aims to update the knowledge about immunity in the pathogenesis of ALD, which may facilitate to enhancement of currently available interventions for ALD treatment.

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Chronic ethanol diet increases regulatory T‐cell activity and inhibits hepatitis C virus core‐specific cellular immune responses in mice

Cited by 11 publications

References 48 publications

Alcohol intake alters immune responses and promotes CNS viral persistence in mice

Alcohol intake alters immune responses and promotes CNS viral persistence in mice

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

Recent Insights Into the Role of Immune Cells in Alcoholic Liver Disease

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