比利时根特大学Charlotte L. Scott课题组近日取得一项新成果。他们揭示骨桥蛋白表达确定了与脂肪肝中与库普弗细胞（KCs）不同的已募集巨噬细胞亚型。该研究于2020年9月3日发表于《免疫》。

他们证明了代谢相关性脂肪肝疾病（MAFLD）中的KCs降低，被源自骨髓的巨噬细胞替代。募集的巨噬细胞存在于两个具有不同激活状态的亚群中，它们要么与稳态KC相似，要么与来自肥胖脂肪组织的脂质相关的巨噬细胞（LAM）相似。肝LAMs表达骨桥蛋白（一种针对非酒精性脂肪性肝炎（NASH）患者的生物标志物），与纤维化的进展有关。与此相吻合的是，在肝脏区域发现的KAM数量减少的LAM表现为Desmin表达增加。

总之，他们的数据突出了巨噬细胞池内相当大的异质性，并表明在MAFLD中需要更特异的巨噬细胞靶向策略。

据悉，MAFLD代表从简单脂肪变性到NASH的一系列疾病状态。肝巨噬细胞，特别是KC，被认为通过其活化在MAFLD的发病机理中起重要作用，尽管这些细胞所起的确切作用仍不清楚。

附：英文原文

Title: Osteopontin Expression Identifies a Subset of Recruited Macrophages Distinct from Kupffer Cells in the Fatty Liver

Author: Anneleen Remmerie, Liesbet Martens, Tinne Thoné, Angela Castoldi, Ruth Seurinck, Benjamin Pavie, Joris Roels, Bavo Vanneste, Sofie De Prijck, Mathias Vanhockerhout, Mushida Binte Abdul Latib, Lindsey Devisscher, Anne Hoorens, Johnny Bonnardel, Niels Vandamme, Anna Kremer, Peter Borghgraef, Hans Van Vlierberghe, Saskia Lippens, Edward Pearce, Yvan Saeys, Charlotte L. Scott

Issue&Volume: 2020-09-03

Abstract: Metabolic-associated fatty liver disease (MAFLD) represents a spectrum of disease states ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic macrophages, specifically Kupffer cells (KCs), are suggested to play important roles in the pathogenesis of MAFLD through their activation, although the exact roles played by these cells remain unclear. Here, we demonstrated that KCs were reduced in MAFLD being replaced by macrophages originating from the bone marrow. Recruited macrophages existed in two subsets with distinct activation states, either closely resembling homeostatic KCs or lipid-associated macrophages (LAMs) from obese adipose tissue. Hepatic LAMs expressed Osteopontin, a biomarker for patients with NASH, linked with the development of fibrosis. Fitting with this, LAMs were found in regions of the liver with reduced numbers of KCs, characterized by increased Desmin expression. Together, our data highlight considerable heterogeneity within the macrophage pool and suggest a need for more specific macrophage targeting strategies in MAFLD.

DOI: 10.1016/j.immuni.2020.08.004

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30357-5