Murine CD103+ dendritic cells protect against steatosis progression towards steatohepatitis
Murine CD103+ dendritic cells protect against steatosis progression towards steatohepatitis
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DOI：
10.1016/j.jhep.2017.01.008
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发表时间：
2017-06-01
影响因子：
25.7
通讯作者：
Lukacs-Kornek, Veronika
中科院分区：
文献类型：
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作者：
Heier, Eva-Carina;Meier, Anna;Lukacs-Kornek, Veronika
背景与目的：非酒精性脂肪肝(NAFL)是代谢综合征的肝脏后果，可进展为非酒精性脂肪性肝炎(NASH)。确定决定NASH进展并导致不可逆转的肝细胞损伤的分子和细胞因素是至关重要的。树突状细胞(DC)是一种异质性细胞，其中CD103(+)DC在免疫耐受中发挥着重要作用。方法：采用多色流式细胞仪、细胞因子和定量聚合酶链式反应技术，对缺乏CD103(+)DC的高蔗糖饮食(HSD)和蛋氨酸胆碱缺乏饮食(MCD)缺乏ATF-like-3(BATF3)缺乏的动物脂肪变性向脂肪性肝炎的进展进行分析。结果：BATF3(-/-)动物的代谢挑战导致脂肪变性向脂肪性肝炎的进展，表现为炎症细胞进入肝脏的增加和髓系细胞在天然刺激下炎性细胞的产生增加。然而，cDC1s的缺失并没有影响细胞的凋亡和纤维化进程，但改变了涉及脂类代谢的基因。将CD103(+)cDC1s过继转移到BATF3缺乏的动物体内，逆转了这些观察到的变化，更重要的是可以减轻已建立的小鼠脂肪性肝炎的细胞损伤和炎症。结论：我们在这里鉴定了小鼠CD103(+)cDC1s是一种保护性DC亚型，影响促抗炎平衡，保护肝脏免受代谢损伤。作为肝脏完整性的守护者，它们在小鼠脂肪性肝炎的发展过程中起着关键作用。非酒精性脂肪肝(NAFL)是代谢综合征的肝脏后果，可导致非酒精性脂肪性肝炎(NASH)。目前的研究表明，在这一过程中，特定的小鼠树突状细胞亚型具有强大的调节作用，可以影响肝脏的炎症环境。(C)2017年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background & Aims: Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic syndrome and can progress to non-alcoholic steatohepatitis (NASH). The identification of molecular and cellular factors that determine the progression of NASH and lead to irreversible hepatocellular damage are crucial. Dendritic cells (DCs) represent a heterogeneous cell population among which CD103(+) DCs play a significant role in immunity and tolerance. We aimed to clarify the role of this DC subset in the pathomechanism of NASH.Methods: Steatosis progression towards steatohepatitis was analysed using multicolor FACS analyses, cytokine and qPCR array in high sucrose diet (HSD) and methionine and choline deficient diet (MCD) fed wild-type and basic leucine zipper transcription factor, ATF-Like-3 (Batf3) deficient animals, which lack CD103(+) DCs (classical type-1 DC, cDC1s).Results: Metabolic challenge of Batf3(-/-) animals resulted in the progression of steatosis towards steatohepatitis, manifesting by an increased influx of inflammatory cells into the liver and elevated inflammatory cytokine production of myeloid cells upon innate stimuli. However, the lack of cDC1s did not affect cellular apoptosis and fibrosis progression but altered genes involved in lipid metabolism. The adoptive transfer of CD103(+) cDC1s to Batf3 deficient animals reversed these observed changes and more importantly could attenuate cellular damage and inflammation in established murine steatohepatitis.Conclusion: Here, we have identified the murine CD103(+) cDC1s as a protective DC subtype that influences the pro-anti-inflammatory balance and protects the liver from metabolic damage. As guardians of liver integrity, they play a key role in the inflammatory process during the development of steatohepatitis in mice.Lay summary: Non-alcoholic fatty liver (NAFL) is the hepatic consequence of metabolic syndrome and can lead to nonalcoholic steatohepatitis (NASH). The current study demonstrated that a specific murine dendritic cell subtype possesses a potent regulatory role to influence the inflammatory milieu of the liver in this process. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.