Department of Forensic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Sci Rep. 2018 Apr 23;8(1):6415. doi: 10.1038/s41598-018-24825-x.
Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy model. In the early phase of DDC-induced cholangiopathy, the number of KCs significantly increased over time. Moreover, KCs were associated with abnormal phenotypic changes in other liver cells, such as hepatocytes, biliary epithelial cells, liver sinusoidal endothelial cells, and hepatic stellate cells. In contrast, KC depletion by clodronate administration suppressed the progression of the disease, and maintained the phenotypes of other cells. In the regression phase, the numbers of KCs significantly decreased, and the cells redifferentiated to their quiescent state. In contrast, KC depletion delayed the recovery of cells by maintaining other liver cells in an active state. These findings suggest that KCs play detrimental roles in the progression phase; however, they are beneficial in the regression phase by mediating interactions between other liver cells. Our data provide new insights into the roles of KCs in the pathogenesis of cholangiopathy.
枯否细胞（KCs）是维持组织内稳态的关键因素，参与多种肝脏疾病的发生。然而，KCs 在胆管病发病机制中的作用在很大程度上尚不清楚。我们旨在研究 KCs 在 3,5-二乙氧羰基-1,4-二氢吡啶（DDC）诱导的胆管病模型的进展和消退阶段中的精确作用。在 DDC 诱导的胆管病的早期阶段，KCs 的数量随时间的推移显著增加。此外，KCs 与其他肝细胞（如肝细胞、胆管上皮细胞、肝窦内皮细胞和肝星状细胞）的异常表型变化有关。相比之下，通过氯膦酸盐给药耗竭 KCs 抑制了疾病的进展，并维持了其他细胞的表型。在消退阶段，KCs 的数量显著减少，细胞重新分化为静止状态。相比之下，耗竭 KCs 通过使其他肝细胞保持活跃状态，从而延迟了细胞的恢复。这些发现表明，KCs 在进展阶段发挥有害作用；然而，它们在消退阶段通过介导其他肝细胞之间的相互作用而有益。我们的数据为 KCs 在胆管病发病机制中的作用提供了新的见解。
