{"title":"Innate immune regulation in inflammation resolution and liver regeneration in drug-induced liver injury.","authors":"Yihan Qian, Jie Zhao, Hailong Wu, Xiaoni Kong","doi":"10.1007/s00204-024-03886-0","DOIUrl":null,"url":null,"abstract":"<p><p>Drug-induced liver injury (DILI) is an acute liver injury that poses a significant threat to human health. In severe cases, it can progress into chronic DILI or even lead to liver failure. DILI is typically caused by either intrinsic hepatotoxicity or idiosyncratic metabolic or immune responses. In addition to the direct damage drugs inflict on hepatocytes, the immune responses and liver inflammation triggered by hepatocyte death can further exacerbate DILI. Initially, we briefly discussed the differences in immune cell activation based on the type of liver cell death (hepatocytes, cholangiocytes, and LSECs). We then focused on the role of various immune cells (including macrophages, monocytes, neutrophils, dendritic cells, liver sinusoidal endothelial cells, eosinophils, natural killer cells, and natural killer T cells) in both the liver injury and liver regeneration stages of DILI. This article primarily reviews the role of innate immune regulation mediated by these immune cells in resolving inflammation and promoting liver regeneration during DILI, as well as therapeutic approaches targeting these immune cells for the treatment of DILI. Finally, we discussed the activation and function of liver progenitor cells (LPCs) during APAP-induced massive hepatic necrosis and the involvement of chronic inflammation in DILI.</p>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00204-024-03886-0","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Drug-induced liver injury (DILI) is an acute liver injury that poses a significant threat to human health. In severe cases, it can progress into chronic DILI or even lead to liver failure. DILI is typically caused by either intrinsic hepatotoxicity or idiosyncratic metabolic or immune responses. In addition to the direct damage drugs inflict on hepatocytes, the immune responses and liver inflammation triggered by hepatocyte death can further exacerbate DILI. Initially, we briefly discussed the differences in immune cell activation based on the type of liver cell death (hepatocytes, cholangiocytes, and LSECs). We then focused on the role of various immune cells (including macrophages, monocytes, neutrophils, dendritic cells, liver sinusoidal endothelial cells, eosinophils, natural killer cells, and natural killer T cells) in both the liver injury and liver regeneration stages of DILI. This article primarily reviews the role of innate immune regulation mediated by these immune cells in resolving inflammation and promoting liver regeneration during DILI, as well as therapeutic approaches targeting these immune cells for the treatment of DILI. Finally, we discussed the activation and function of liver progenitor cells (LPCs) during APAP-induced massive hepatic necrosis and the involvement of chronic inflammation in DILI.
药物性肝损伤(DILI)是一种急性肝损伤,对人类健康构成重大威胁。严重者可发展为慢性 DILI,甚至导致肝功能衰竭。DILI 通常是由内在肝毒性或特异性代谢或免疫反应引起的。除了药物对肝细胞造成的直接损伤外,肝细胞死亡引发的免疫反应和肝脏炎症也会进一步加剧 DILI。首先,我们简要讨论了肝细胞死亡类型(肝细胞、胆管细胞和LSECs)在免疫细胞激活方面的差异。然后,我们重点讨论了各种免疫细胞(包括巨噬细胞、单核细胞、中性粒细胞、树突状细胞、肝窦内皮细胞、嗜酸性粒细胞、自然杀伤细胞和自然杀伤 T 细胞)在 DILI 的肝损伤和肝再生阶段的作用。本文主要综述了这些免疫细胞介导的先天性免疫调节在 DILI 期间消除炎症和促进肝脏再生中的作用,以及针对这些免疫细胞治疗 DILI 的方法。最后,我们讨论了在 APAP 诱导的大量肝坏死过程中肝脏祖细胞(LPCs)的活化和功能,以及慢性炎症在 DILI 中的参与。
期刊介绍:
Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.