Subacute dibutyl phthalate exposure impairs hepatic T cells and facilitates hepatitis B progression in mouse liver
The hepatic immune microenvironment governs liver disease susceptibility by balancing immune defense and tolerance. While phthalate esters (PAEs), emerging pollutants derived from plastics, have been acknowledged as hepatoxic substances, the immunomodulatory and clinical impacts of subacute PAEs exp...
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Elsevier
2025-07-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325007341 |
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| author | Zhenru Zhu Dongli Linghu Yongyi Luo Shibo Sun Zheng Xie Zhichao Sun Chuanjiang Li Qifan Zhang Qiwei Yao Dehua Wu Chuanhui Cao Jingyuan Sun |
| author_facet | Zhenru Zhu Dongli Linghu Yongyi Luo Shibo Sun Zheng Xie Zhichao Sun Chuanjiang Li Qifan Zhang Qiwei Yao Dehua Wu Chuanhui Cao Jingyuan Sun |
| author_sort | Zhenru Zhu |
| collection | DOAJ |
| description | The hepatic immune microenvironment governs liver disease susceptibility by balancing immune defense and tolerance. While phthalate esters (PAEs), emerging pollutants derived from plastics, have been acknowledged as hepatoxic substances, the immunomodulatory and clinical impacts of subacute PAEs exposure remain underexplored. In this study, we identified dibutyl phthalate (DBP) as a predominant PAE in liver tissues from hepatitis B virus (HBV)-infected patients. Based on the murine model mimicking specific scenarios of subacute DBP exposure, single-cell RNA sequencing and flow cytometry revealed that DBP significantly depleted hepatic T cells and induced functional exhaustion. Moreover, HBV-carrier mice exposed to DBP sub-acutely exhibited prolonged viral persistence, delayed HBsAg clearance and heightened liver injury markers. The co-culture assays mechanistically linked the persistent HBV infection to T cell dysfunction in the context of DBP exposure. Epidemiological analyses further correlated elevated urinary DBP metabolites with increased positivity of HBV indicators. Among individuals with HBV infection history, higher DBP metabolite levels were associated with reduced liver function. In conclusion, our findings elucidated that subacute DBP exposure exacerbates HBV progression by driving T cell exhaustion and synergistically leading to the collapse of hepatic immune microenvironment. Therefore, we propose DBP as a facilitator of HBV, positioning subacute DBP exposure as risk factors for viral hepatitis, advocating for monitoring of PAEs in high-risk populations and therapeutic strategies targeting immune exhaustion to mitigate PAEs-viral synergism in liver diseases. |
| format | Article |
| id | doaj-art-060bd12066764b9c92065a6b9727a7d5 |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-060bd12066764b9c92065a6b9727a7d52025-08-20T02:02:51ZengElsevierEcotoxicology and Environmental Safety0147-65132025-07-0129911839810.1016/j.ecoenv.2025.118398Subacute dibutyl phthalate exposure impairs hepatic T cells and facilitates hepatitis B progression in mouse liverZhenru Zhu0Dongli Linghu1Yongyi Luo2Shibo Sun3Zheng Xie4Zhichao Sun5Chuanjiang Li6Qifan Zhang7Qiwei Yao8Dehua Wu9Chuanhui Cao10Jingyuan Sun11Pingshan Hospital, Southern Medical University, Shenzhen, Guangdong, PR China; Pingshan District Peoples’ Hospital of Shenzhen, Shenzhen, Guangdong, PR China; Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, PR ChinaDepartment of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, PR ChinaDepartment of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, PR ChinaDivision of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, PR ChinaDepartment of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, PR ChinaDepartment of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, PR ChinaDivision of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, PR ChinaDivision of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, PR ChinaDepartment of Radiation Oncology, Fujian Cancer Hospital, Clinical Oncology School of Fujian Medical University, Fuzhou, PR China; Corresponding author.Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China; Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangzhou, Guangdong, PR China; Correspondence to: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China; Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Guangzhou, Guangdong, PR China; Correspondence to: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China; Correspondence to: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China.The hepatic immune microenvironment governs liver disease susceptibility by balancing immune defense and tolerance. While phthalate esters (PAEs), emerging pollutants derived from plastics, have been acknowledged as hepatoxic substances, the immunomodulatory and clinical impacts of subacute PAEs exposure remain underexplored. In this study, we identified dibutyl phthalate (DBP) as a predominant PAE in liver tissues from hepatitis B virus (HBV)-infected patients. Based on the murine model mimicking specific scenarios of subacute DBP exposure, single-cell RNA sequencing and flow cytometry revealed that DBP significantly depleted hepatic T cells and induced functional exhaustion. Moreover, HBV-carrier mice exposed to DBP sub-acutely exhibited prolonged viral persistence, delayed HBsAg clearance and heightened liver injury markers. The co-culture assays mechanistically linked the persistent HBV infection to T cell dysfunction in the context of DBP exposure. Epidemiological analyses further correlated elevated urinary DBP metabolites with increased positivity of HBV indicators. Among individuals with HBV infection history, higher DBP metabolite levels were associated with reduced liver function. In conclusion, our findings elucidated that subacute DBP exposure exacerbates HBV progression by driving T cell exhaustion and synergistically leading to the collapse of hepatic immune microenvironment. Therefore, we propose DBP as a facilitator of HBV, positioning subacute DBP exposure as risk factors for viral hepatitis, advocating for monitoring of PAEs in high-risk populations and therapeutic strategies targeting immune exhaustion to mitigate PAEs-viral synergism in liver diseases.http://www.sciencedirect.com/science/article/pii/S0147651325007341DBPSingle-cell RNA sequencingLiver immune exhaustionT lymphocytesHepatitis B |
| spellingShingle | Zhenru Zhu Dongli Linghu Yongyi Luo Shibo Sun Zheng Xie Zhichao Sun Chuanjiang Li Qifan Zhang Qiwei Yao Dehua Wu Chuanhui Cao Jingyuan Sun Subacute dibutyl phthalate exposure impairs hepatic T cells and facilitates hepatitis B progression in mouse liver Ecotoxicology and Environmental Safety DBP Single-cell RNA sequencing Liver immune exhaustion T lymphocytes Hepatitis B |
| title | Subacute dibutyl phthalate exposure impairs hepatic T cells and facilitates hepatitis B progression in mouse liver |
| title_full | Subacute dibutyl phthalate exposure impairs hepatic T cells and facilitates hepatitis B progression in mouse liver |
| title_fullStr | Subacute dibutyl phthalate exposure impairs hepatic T cells and facilitates hepatitis B progression in mouse liver |
| title_full_unstemmed | Subacute dibutyl phthalate exposure impairs hepatic T cells and facilitates hepatitis B progression in mouse liver |
| title_short | Subacute dibutyl phthalate exposure impairs hepatic T cells and facilitates hepatitis B progression in mouse liver |
| title_sort | subacute dibutyl phthalate exposure impairs hepatic t cells and facilitates hepatitis b progression in mouse liver |
| topic | DBP Single-cell RNA sequencing Liver immune exhaustion T lymphocytes Hepatitis B |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325007341 |
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