Hepatic Lamp2a deficiency promotes inflammation of murine autoimmune cholangitis via affecting bile acid metabolism
Summary: Primary biliary cholangitis is characterized by breaking of immune tolerance and disorders of bile acid metabolism. Our previous study found that abnormal expression of Lamp2 was detected in PBC patients. However, the specific role of Lamp2a in disease progression is still unclear. In this...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225000641 |
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| author | Qingling Fan Guanya Guo Yinan Hu Yi Lu Rui Su Jiaqi Yang Erzhuo Xia Shuoyi Ma Miao Zhang Jingbo Wang Ting Li Ying Han |
| author_facet | Qingling Fan Guanya Guo Yinan Hu Yi Lu Rui Su Jiaqi Yang Erzhuo Xia Shuoyi Ma Miao Zhang Jingbo Wang Ting Li Ying Han |
| author_sort | Qingling Fan |
| collection | DOAJ |
| description | Summary: Primary biliary cholangitis is characterized by breaking of immune tolerance and disorders of bile acid metabolism. Our previous study found that abnormal expression of Lamp2 was detected in PBC patients. However, the specific role of Lamp2a in disease progression is still unclear. In this study, we showed that hepatic-specific Lamp2a deficiency could aggravate the inflammatory phenotype of murine autoimmune cholangitis. Mechanistically, the loss of Lamp2a in hepatocytes contributed to the abnormal accumulation of Acot8, thus altered the bile acid components, thereby enhancing the lymphocyte activities, and ultimately promoting the inflammatory phenotype of model mice. Moreover, we also found that Acot8 knockdown could alleviate the liver inflammation caused by Lamp2a deficiency. Altogether, our findings explored the effect of Lamp2a deficiency on the murine autoimmune cholangitis by the perspective of bile acid metabolism, and marked the possibility of Acot8 as a new target for the treatment of PBC disease. |
| format | Article |
| id | doaj-art-408703d533a14d4b97e28c50b982d58d |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-408703d533a14d4b97e28c50b982d58d2025-02-10T04:34:44ZengElsevieriScience2589-00422025-02-01282111804Hepatic Lamp2a deficiency promotes inflammation of murine autoimmune cholangitis via affecting bile acid metabolismQingling Fan0Guanya Guo1Yinan Hu2Yi Lu3Rui Su4Jiaqi Yang5Erzhuo Xia6Shuoyi Ma7Miao Zhang8Jingbo Wang9Ting Li10Ying Han11Xijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, ChinaXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, ChinaXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, ChinaXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, ChinaXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, ChinaXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, ChinaXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, ChinaXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, ChinaXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, ChinaXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, China; Corresponding authorXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, China; Corresponding authorXijing Hospital of Digestive Diseases, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi’an 710032, China; Corresponding authorSummary: Primary biliary cholangitis is characterized by breaking of immune tolerance and disorders of bile acid metabolism. Our previous study found that abnormal expression of Lamp2 was detected in PBC patients. However, the specific role of Lamp2a in disease progression is still unclear. In this study, we showed that hepatic-specific Lamp2a deficiency could aggravate the inflammatory phenotype of murine autoimmune cholangitis. Mechanistically, the loss of Lamp2a in hepatocytes contributed to the abnormal accumulation of Acot8, thus altered the bile acid components, thereby enhancing the lymphocyte activities, and ultimately promoting the inflammatory phenotype of model mice. Moreover, we also found that Acot8 knockdown could alleviate the liver inflammation caused by Lamp2a deficiency. Altogether, our findings explored the effect of Lamp2a deficiency on the murine autoimmune cholangitis by the perspective of bile acid metabolism, and marked the possibility of Acot8 as a new target for the treatment of PBC disease.http://www.sciencedirect.com/science/article/pii/S2589004225000641InmunologyTranscriptomics |
| spellingShingle | Qingling Fan Guanya Guo Yinan Hu Yi Lu Rui Su Jiaqi Yang Erzhuo Xia Shuoyi Ma Miao Zhang Jingbo Wang Ting Li Ying Han Hepatic Lamp2a deficiency promotes inflammation of murine autoimmune cholangitis via affecting bile acid metabolism iScience Inmunology Transcriptomics |
| title | Hepatic Lamp2a deficiency promotes inflammation of murine autoimmune cholangitis via affecting bile acid metabolism |
| title_full | Hepatic Lamp2a deficiency promotes inflammation of murine autoimmune cholangitis via affecting bile acid metabolism |
| title_fullStr | Hepatic Lamp2a deficiency promotes inflammation of murine autoimmune cholangitis via affecting bile acid metabolism |
| title_full_unstemmed | Hepatic Lamp2a deficiency promotes inflammation of murine autoimmune cholangitis via affecting bile acid metabolism |
| title_short | Hepatic Lamp2a deficiency promotes inflammation of murine autoimmune cholangitis via affecting bile acid metabolism |
| title_sort | hepatic lamp2a deficiency promotes inflammation of murine autoimmune cholangitis via affecting bile acid metabolism |
| topic | Inmunology Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225000641 |
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