Osteopontin Expression Identifies a Subset of Recruited Macrophages Distinct from Kupffer Cells in the Fatty Liver.
Osteopontin Expression Identifies a Subset of Recruited Macrophages Distinct from Kupffer Cells in the Fatty Liver.
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DOI：
10.1016/j.immuni.2020.08.004
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发表时间：
2020-09-15
期刊：
影响因子：
32.4
通讯作者：
Scott CL
中科院分区：
文献类型：
--
作者：
Remmerie A;Martens L;Thoné T;Castoldi A;Seurinck R;Pavie B;Roels J;Vanneste B;De Prijck S;Vanhockerhout M;Binte Abdul Latib M;Devisscher L;Hoorens A;Bonnardel J;Vandamme N;Kremer A;Borghgraef P;Van Vlierberghe H;Lippens S;Pearce E;Saeys Y;Scott CL
代谢相关性脂肪肝病（MAFLD）代表了从单纯性脂肪变性到非酒精性脂肪性肝炎（NASH）的一系列疾病状态。肝巨噬细胞，特别是枯否细胞（KCs），建议发挥重要作用的发病机制中的MAFLD通过其激活，虽然这些细胞发挥的确切作用仍不清楚。在这里，我们证明了在MAFLD中KCs被来自骨髓的巨噬细胞所取代。招募的巨噬细胞存在于两个亚群中，具有不同的激活状态，非常类似于来自肥胖脂肪组织的稳态KC或脂质相关巨噬细胞（LAM）。肝LAMs表达骨桥蛋白，这是NASH患者的生物标志物，与纤维化的发展有关。与此相适应，在具有减少数量的KC的肝脏区域中发现了LAM，其特征在于结蛋白表达增加。总之，我们的数据强调了巨噬细胞库中相当大的异质性，并表明MAFLD需要更具体的巨噬细胞靶向策略。在MAFLD中，常驻KC随时间丢失常驻KC被骨髓来源的巨噬细胞的不同子集取代一个被称为肝LAMs的招募的巨噬细胞的子集表达骨桥蛋白肝LAMs被发现在以结蛋白表达增加为特征的区域中肝巨噬细胞被认为在脂肪肝疾病的发病机制中起关键作用;然而，巨噬细胞池内的异质性在很大程度上仍未研究。在这个问题的免疫力，Remmerie等人。报道了一群骨桥蛋白表达巨噬细胞在脂肪肝中具有独特的转录谱和位置。
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. Resident KCs are lost with time in MAFLD Resident KCs are replaced by distinct subsets of bone marrow derived macrophages One subset of recruited macrophages termed hepatic LAMs, express Osteopontin Hepatic LAMs are found in zones characterized by increased Desmin expression Hepatic macrophages are thought to play key roles in the pathogenesis of fatty liver disease; however, heterogeneity within the macrophage pool remains largely unstudied. In this issue of Immunity, Remmerie et al. report a population of osteopontin-expressing macrophages with a unique transcriptional profile and location in the fatty liver.
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影响因子：
64.8
作者：
Halpern KB;Shenhav R;Matcovitch-Natan O;Toth B;Lemze D;Golan M;Massasa EE;Baydatch S;Landen S;Moor AE;Brandis A;Giladi A;Avihail AS;David E;Amit I;Itzkovitz S
通讯作者：
Itzkovitz S
影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
5.1
作者：
Glass O;Henao R;Patel K;Guy CD;Gruss HJ;Syn WK;Moylan CA;Streilein R;Hall R;Mae Diehl A;Abdelmalek MF
通讯作者：
Abdelmalek MF
影响因子：
9.8
作者：
Buzzetti, Elena;Pinzani, Massimo;Tsochatzis, Emmanuel A.
通讯作者：
Tsochatzis, Emmanuel A.