Devisscher Lindsey, Scott Charlotte L, Lefere Sander, Raevens Sarah, Bogaerts Eliene, Paridaens Annelies, Verhelst Xavier, Geerts Anja, Guilliams Martin, Van Vlierberghe Hans
Department of Gastroenterology and Hepatology, Ghent University, Belgium.
Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB-UGent Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, UK.
Cell Immunol. 2017 Dec;322:74-83. doi: 10.1016/j.cellimm.2017.10.006. Epub 2017 Oct 16.
Kupffer cells (KCs) and monocyte-derived macrophages are implicated in non-alcoholic steatohepatitis (NASH) pathogenesis but their functions remain unclear due to the lack of specific markers to distinguish between the different cell types. Additionally, it is unclear if multiple subsets of KCs are present during NASH. Here, we characterized the liver macrophage subsets during methionine/choline deficient (MCD) diet-induced NASH and recovery. We observed a significant reduced contribution of Ly6CClec4FTim4KCs to the hepatic macrophage pool in MCD fed mice, which normalized during recovery. Ly6CClec4FTim4 monocyte-derived macrophages increased during MCD feeding and returned to baseline during recovery. Ly6CClec4FTim4 monocyte-derived KCs developed during initial recovery but did not self-renew as their numbers were reduced after full recovery. Initial recovery from MCD diet feeding was further characterized by increased proportions of Ki-67 proliferating KCs. In conclusion, the hepatic macrophage pool undergoes substantial albeit transient changes during NASH and recovery, with the KC pool being maintained by proliferation and differentiation of short-lived monocyte-derived KCs.
库普弗细胞（KCs）和单核细胞衍生的巨噬细胞与非酒精性脂肪性肝炎（NASH）的发病机制有关，但由于缺乏区分不同细胞类型的特异性标志物，它们的功能仍不清楚。此外，尚不清楚在NASH期间是否存在多个KCs亚群。在这里，我们对蛋氨酸/胆碱缺乏（MCD）饮食诱导的NASH及恢复过程中的肝脏巨噬细胞亚群进行了表征。我们观察到，在喂食MCD的小鼠中，Ly6C⁺Clec4F⁺Tim4⁺ KCs对肝脏巨噬细胞池的贡献显著降低，在恢复过程中恢复正常。Ly6C⁺Clec4F⁺Tim4⁺单核细胞衍生的巨噬细胞在MCD喂养期间增加，并在恢复过程中恢复到基线水平。Ly6C⁺Clec4F⁺Tim4⁺单核细胞衍生的KCs在初始恢复期间出现，但没有自我更新，因为在完全恢复后它们的数量减少了。从MCD饮食喂养中初步恢复的特征还包括Ki-67增殖性KCs比例增加。总之，在NASH和恢复过程中，肝脏巨噬细胞池发生了显著的、尽管是短暂的变化，KCs池由短命的单核细胞衍生的KCs的增殖和分化维持。
