Cholesterol accumulation on dendritic cells reverses chronic hepatitis B virus infection-induced dysfunction

Zhao, Huajun; Yu, Yating; Wang, Yucan; Zhao, Lianhui; Yang, Ailu; Hu, Yifei; Pan, Zhaoyi; Wang, Zixuan; Yang, Jing; Han, Qiuju; Tian, Zhigang; Zhang, Jian

doi:10.1038/s41423-022-00939-1

Cited by 11 publications

(13 citation statements)

References 60 publications

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“…The effects of MCD in DC–T cell interaction are also observed by other groups 79–81 . Importantly, the reduction of cell surface cholesterol in DCs impairs their function against promoting the clearance of Toxoplasma gondii and hepatitis B virus in vivo, 82,83 highlighting that cholesterol in the plasma membrane serves important roles in facilitating T‐cell priming and adaptive immune responses. Further, APOE (encoded by Apoe ) is an important cholesterol and lipid carrier, Apoe ‐deficient primary splenic DCs accumulate more intracellular cholesterol.…”

Section: Cholesterol and Its Metabolitesmentioning

confidence: 57%

“…75,76 The effects of MCD in DC-T cell interaction are also observed by other groups. [79][80][81] Importantly, the reduction of cell surface cholesterol in DCs impairs their function against promoting the clearance of Toxoplasma gondii and hepatitis B virus in vivo, 82,83 highlighting that cholesterol in the plasma membrane serves important roles in Beyond regulation of signal 1, additional studies have shown that cholesterol levels can influence DC migration and cytokine production. Indeed, increasing cholesterol levels using a high-cholesterol diet or ablation of Apoe in mice dampens the migration of DCs to the lymph node, lowering cholesterol levels can partially reverse these migration defects.…”

Section: Cholesterolmentioning

confidence: 99%

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Lipid metabolism in dendritic cell biology

You

Chi

2023

Immunological Reviews

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SummaryDendritic cells (DCs) are innate immune cells that detect and process environmental signals and communicate them with T cells to bridge innate and adaptive immunity. Immune signals and microenvironmental cues shape the function of DC subsets in different contexts, which is associated with reprogramming of cellular metabolic pathways. In addition to integrating these extracellular cues to meet bioenergetic and biosynthetic demands, cellular metabolism interplays with immune signaling to shape DC‐dependent immune responses. Emerging evidence indicates that lipid metabolism serves as a key regulator of DC responses. Here, we summarize the roles of fatty acid and cholesterol metabolism, as well as selective metabolites, in orchestrating the functions of DCs. Specifically, we highlight how different lipid metabolic programs, including de novo fatty acid synthesis, fatty acid β oxidation, lipid storage, and cholesterol efflux, influence DC function in different contexts. Further, we discuss how dysregulation of lipid metabolism shapes DC intracellular signaling and contributes to the impaired DC function in the tumor microenvironment. Finally, we conclude with a discussion on key future directions for the regulation of DC biology by lipid metabolism. Insights into the connections between lipid metabolism and DC functional specialization may facilitate the development of new therapeutic strategies for human diseases.

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Section: Cholesterol and Its Metabolitesmentioning

confidence: 57%

Section: Cholesterolmentioning

confidence: 99%

Lipid metabolism in dendritic cell biology

You

Chi

2023

Immunological Reviews

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“…85 Lipophilic statin treatment with HBV vaccine promoted cholesterol accumulation and formation of lipid rafts on dendritic cell (DC) in HBV-carrier mice, which enhanced viral clearance. 86 This increase in free cholesterol for DCs has been postulated to be another mechanism for statin's antiproliferative property in HCC. 86 Treatment with rosuvastatin in HBV not only increased quantity of natural killer (NK) cells promoting viral clearance, but also suppressed T-cell immunoglobulin and mucin-containing domain 3 (TIM-3) leading to upregulation of cell-mediated immunity and Th1 response.…”

Section: Mechanism Of Statin In Viral Hepatitismentioning

confidence: 99%

“…86 This increase in free cholesterol for DCs has been postulated to be another mechanism for statin's antiproliferative property in HCC. 86 Treatment with rosuvastatin in HBV not only increased quantity of natural killer (NK) cells promoting viral clearance, but also suppressed T-cell immunoglobulin and mucin-containing domain 3 (TIM-3) leading to upregulation of cell-mediated immunity and Th1 response. [87][88][89] The combined effects on NK proliferation and TIM-3 mediated the antiviral activity and antiproliferation of HCC in patients with HBV.…”

Section: Mechanism Of Statin In Viral Hepatitismentioning

confidence: 99%

Statins in Chronic Liver Disease: Review of the Literature and Future Role

Pham,

Benhammou

2024

Semin Liver Dis

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Chronic liver disease (CLD) is a major contributor to global mortality, morbidity, and healthcare burden. Progress in pharmacotherapeutic for CLD management is lagging given its impact on the global population. While statins are indicated for the management of dyslipidemia and cardiovascular disease, their role in CLD prevention and treatment is emerging. Beyond their lipid lowering effects, their liver-related mechanisms of action are multifactorial and include anti-inflammatory, anti-proliferative, and immune-protective effects. In this review, we highlight what is known about the clinical benefits of statins in viral and non-viral etiologies of CLD and HCC, and explore key mechanisms and pathways targeted by statins. While their benefits may span the spectrum of CLD and potentially HCC treatment, their role in CLD chemoprevention is likely to have the largest impact. As emerging data suggest that genetic variants may impact their benefits, the role of statins in precision hepatology will need to be further explored.

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“…Altered availability of cholesterol during infection may influence the antiviral immune response [ 136 ]. Highlighting this aspect of liver immunology is the recent evidence that manipulating the level and distribution of cholesterol in T cells and dendritic cell membranes can influence their level of anti-HBV activity [ 137 , 138 ].…”

Section: Hepatic T Cell Subsets During Chronic Viral Hepatitismentioning

confidence: 99%

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

2023

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T cells play an important role in the clearance of hepatotropic viruses but may also cause liver injury and contribute to disease progression in chronic hepatitis B and C virus infections which affect millions of people worldwide. The liver provides a unique microenvironment of immunological tolerance and hepatic immune regulation can modulate the functional properties of T cell subsets and influence the outcome of a virus infection. Extensive research over the last years has advanced our understanding of hepatic conventional CD4+ and CD8+ T cells and unconventional T cell subsets and their functions in the liver environment during acute and chronic viral infections. The recent development of new small animal models and technological advances should further increase our knowledge of hepatic immunological mechanisms. Here we provide an overview of the existing models to study hepatic T cells and review the current knowledge about the distinct roles of heterogeneous T cell populations during acute and chronic viral hepatitis.

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Cholesterol accumulation on dendritic cells reverses chronic hepatitis B virus infection-induced dysfunction

Cited by 11 publications

References 60 publications

Lipid metabolism in dendritic cell biology

Lipid metabolism in dendritic cell biology

Statins in Chronic Liver Disease: Review of the Literature and Future Role

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

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