文献类型：期刊文献

英文题名：Tissue-resident trained immunity in hepatocytes protects against septic liver injury in zebrafish

作者：Wang, Zhuang[1];Liu, Yuanyuan[1];Hu, Jing[1];You, Xinwei[1];Yang, Jin[1];Zhang, Yuanxing[2];Liu, Qin[1,3];Yang, Dahai[1,3]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Lab Aquat Anim Dis, Shanghai 200237, Peoples R China;[2]Southern Marine Sci & Engn Guangdong Lab Zhuhai, Zhuhai, Peoples R China;[3]Shanghai Engn Res Ctr Maricultured Anim Vaccines, Shanghai 200237, Peoples R China

年份：2024

卷号：43

期号：6

外文期刊名：CELL REPORTS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001263755000001)】；

基金：Acknowledgments This work was supported by the National Natural Science Foundation of China (32122090) , the National Key Research and Development Program of China (2022YFD2402000 and 2022YFC2804300) , and the Fundamental Research Funds for the Central Universities (222201231733) .

语种：英文

摘要：Trained immunity is classically characterized by long-term functional reprogramming of innate immune cells to combat infectious diseases. Infection -induced organ injury is a common clinical severity phenotype of sepsis. However, whether the induction of trained immunity plays a role in protecting septic organ injury remains largely unknown. Here, through establishing an in vivo b-glucan training and lipopolysaccharide (LPS) challenge model in zebrafish larvae, we observe that induction of trained immunity could inhibit pyroptosis of hepatocytes to alleviate septic liver injury, with an elevated trimethyl-histone H3 lysine 4 (H3K4me3) modification that targets mitophagy-related genes. Moreover, we identify a C -type lectin domain receptor in zebrafish, named Dr Dectin-1, which is revealed as the orchestrator in gating H3K4me3 rewiring -mediated mitophagy activation and alleviating pyroptosis-engaged septic liver injury in vivo . Taken together, our results uncover tissue -resident trained immunity in maintaining liver homeostasis at the whole -animal level and offer an in vivo model to efficiently integrate trained immunity for immunotherapies.