The downregulation of Tapasin in dendritic cell regulates CD8+ T cell autophagy to hamper hepatitis B viral clearance in the induced pluripotent stem cell-derived hepatocyte organoid
© 2024 Wiley Periodicals LLC..
Tapasin, a crucial molecular chaperone involved viral antigen processing and presentation, plays an important role in antivirus immunity. However, its impact on T cell differentiation in the context of virus clearance remains unclear. In this study, we employed induced pluripotent stem cells to differentiate into hepatocyte-like cell, which were subsequently inserted to the inverted colloidal crystal scaffolds, thus establishing a hepatocyte organoid (HO). By inoculating hepatitis B virus (HBV) particles in the system, we successfully engineered a robust in vitro HBV infection model for at least 3 weeks. Furthermore, we aimed to explore the effects of lentivirus-mediated short hairpin RNA (shRNA) targeting human Tapasin on the differentiation and antiviral function of CD8+ T cells. Specifically, we transfected dendritic cells (DCs) with Tapasin-shRNA and cocultured with T cells. The results demonstrated that Tapasin-shRNA transfected DCs effectively suppressed T cell proliferation and impeded HBV-specific cytotoxic T lymphocyte responses. Our investigation also revealed the role of mTOR pathway activation in reducing autophagy activity within CD8+ T cells. Expressions of autophagy-related proteins, beclin-1, LC3II/LC3I were decreased and PI3K/AKT/mTOR activity was increased in Tapasin-shRNA group. Collectively, our findings elucidate that shRNA targeting the Tapasin gene within DCs inhibits T cell differentiation by reducing autophagy activity to hamper viral clearance in the HBV-infected HO.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:96 |
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| Enthalten in: |
Journal of medical virology - 96(2024), 3 vom: 01. März, Seite e29546 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chen, Jinmei [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 04.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/jmv.29546 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 4 | |a The downregulation of Tapasin in dendritic cell regulates CD8+ T cell autophagy to hamper hepatitis B viral clearance in the induced pluripotent stem cell-derived hepatocyte organoid |
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| 520 | |a Tapasin, a crucial molecular chaperone involved viral antigen processing and presentation, plays an important role in antivirus immunity. However, its impact on T cell differentiation in the context of virus clearance remains unclear. In this study, we employed induced pluripotent stem cells to differentiate into hepatocyte-like cell, which were subsequently inserted to the inverted colloidal crystal scaffolds, thus establishing a hepatocyte organoid (HO). By inoculating hepatitis B virus (HBV) particles in the system, we successfully engineered a robust in vitro HBV infection model for at least 3 weeks. Furthermore, we aimed to explore the effects of lentivirus-mediated short hairpin RNA (shRNA) targeting human Tapasin on the differentiation and antiviral function of CD8+ T cells. Specifically, we transfected dendritic cells (DCs) with Tapasin-shRNA and cocultured with T cells. The results demonstrated that Tapasin-shRNA transfected DCs effectively suppressed T cell proliferation and impeded HBV-specific cytotoxic T lymphocyte responses. Our investigation also revealed the role of mTOR pathway activation in reducing autophagy activity within CD8+ T cells. Expressions of autophagy-related proteins, beclin-1, LC3II/LC3I were decreased and PI3K/AKT/mTOR activity was increased in Tapasin-shRNA group. Collectively, our findings elucidate that shRNA targeting the Tapasin gene within DCs inhibits T cell differentiation by reducing autophagy activity to hamper viral clearance in the HBV-infected HO | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a T cell differentiation | |
| 650 | 4 | |a Tapasin | |
| 650 | 4 | |a autophagy | |
| 650 | 4 | |a hepatitis B virus | |
| 650 | 4 | |a hepatocyte organoid | |
| 650 | 7 | |a Hepatitis B Core Antigens |2 NLM | |
| 650 | 7 | |a Membrane Transport Proteins |2 NLM | |
| 650 | 7 | |a Phosphatidylinositol 3-Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.1.- |2 NLM | |
| 650 | 7 | |a RNA, Small Interfering |2 NLM | |
| 650 | 7 | |a tapasin |2 NLM | |
| 650 | 7 | |a TOR Serine-Threonine Kinases |2 NLM | |
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| 700 | 1 | |a Shen, Leer |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Qingxin |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Siyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Lihong |e verfasserin |4 aut | |
| 700 | 1 | |a Ng, Soon Seng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiaohua |e verfasserin |4 aut | |
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