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XCR1+1型常规树突状细胞在非酒精性脂肪性肝炎中驱动肝脏病理
作者:小柯机器人 发布时间:2021/5/23 21:49:13

以色列魏茨曼科学研究所Ido Amit等研究人员合作发现,XCR1+1型常规树突状细胞在非酒精性脂肪性肝炎(NAFLD)中驱动肝脏病理。2021年5月20日,《自然—医学》杂志在线发表了这一最新研究成果。

研究人员使用单细胞转录组学分析全面概述了非酒精性脂肪性肝炎(NASH)期间小鼠肝脏的免疫组成。研究人员确定了肝脏常规树突状细胞(cDC)与病理学相关的显著增加,并进一步将其来源定义为NASH诱导的cDC祖细胞在骨髓循环中的增强。在NAFLD/NASH中对患者的血液和肝脏进行分析表明,1型cDC(cDC1)更为丰富并在疾病中被激活。

从引流肝脏的淋巴结中进行物理相互作用的cDC-T细胞测序表明,NASH中的cDC促进了炎症性T细胞的重编程,而这先前与NASH恶化有关。最后,在XCR1DTA小鼠中使用cDC1耗竭或使用抗XCL1阻断抗体可减轻NASH小鼠模型中的肝脏病理。总体而言,这项研究提供了NASH中cDC生物学的全面表征,并将XCR1+cDC1鉴定为肝脏病理的重要驱动因素。

据介绍,NAFLD和NASH是普遍存在的肝脏疾病,也是威胁生命的肝硬化、肝衰竭和肝癌发展的基础。慢性坏死性炎症是NASH发展的关键因素,但对该疾病免疫失调的细胞和分子机制知之甚少。

附:英文原文

Title: XCR1 + type 1 conventional dendritic cells drive liver pathology in non-alcoholic steatohepatitis

Author: Aleksandra Deczkowska, Eyal David, Pierluigi Ramadori, Dominik Pfister, Michael Safran, Baoguo At the, Amir Giladi, Diego Adhemar Jaitin, Oren Barboy, Merav Cohen, Ido Yofe, Chamutal Gur, Shir Shlomi-Loubaton, Sandrine Henri, Yousuf Suhail, Mengjie Qiu, Shing Kam, Hila Hermon, Eylon Lahat, Gil Ben Yakov, Oranit Cohen-Ezra, Yana Davidov, Mariya Likhter, David Goitein, Susanne Roth, Achim Weber, Bernard Malissen, Assaf Weiner, Ziv Ben-Ari, Mathias Heikenwlder, Eran Elinav, Ido Amit

Issue&Volume: 2021-05-20

Abstract: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are prevalent liver conditions that underlie the development of life-threatening cirrhosis, liver failure and liver cancer. Chronic necro-inflammation is a critical factor in development of NASH, yet the cellular and molecular mechanisms of immune dysregulation in this disease are poorly understood. Here, using single-cell transcriptomic analysis, we comprehensively profiled the immune composition of the mouse liver during NASH. We identified a significant pathology-associated increase in hepatic conventional dendritic cells (cDCs) and further defined their source as NASH-induced boost in cycling of cDC progenitors in the bone marrow. Analysis of blood and liver from patients on the NAFLD/NASH spectrum showed that type 1 cDCs (cDC1) were more abundant and activated in disease. Sequencing of physically interacting cDC-T cell pairs from liver-draining lymph nodes revealed that cDCs in NASH promote inflammatory T cell reprogramming, previously associated with NASH worsening. Finally, depletion of cDC1 in XCR1DTA mice or using anti-XCL1-blocking antibody attenuated liver pathology in NASH mouse models. Overall, our study provides a comprehensive characterization of cDC biology in NASH and identifies XCR1+ cDC1 as an important driver of liver pathology.

DOI: 10.1038/s41591-021-01344-3

Source: https://www.nature.com/articles/s41591-021-01344-3

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex