Dual role of neutrophils in modulating liver injury and fibrosis during development and resolution of diet-induced murine steatohepatitis.
Dual role of neutrophils in modulating liver injury and fibrosis during development and resolution of diet-induced murine steatohepatitis.
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中性粒细胞在饮食诱导的小鼠脂肪性肝炎发生和消退过程中调节肝损伤和纤维化的双重作用。
DOI：
10.1038/s41598-021-03679-w
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发表时间：
2021-12-17
影响因子：
4.6
通讯作者：
Feldstein AE
中科院分区：
文献类型：
--
作者：
Kim AD;Kim SE;Leszczynska A;Kaufmann B;Reca A;Kim DJ;Feldstein AE
肝脏中的炎症变化代表非酒精性脂肪性肝炎（NASH）的关键特征，非酒精性脂肪性肝病（NAFLD）的进行性形式。先天性免疫激活（包括肝嗜中性粒细胞浸润）是重要的炎症触发因素，也是炎症消退的潜在介质。在这项研究中，我们通过抗淋巴细胞抗原6复合基因座G6 D（Ly 6 G）抗体的管理过程中正在进行的高脂肪-果糖-胆固醇（FFC）饮食诱导的小鼠NASH中性粒细胞耗竭的影响，并在炎症解决切换到低脂对照饮食。在NASH进展过程中，保护作用表现为HSC活化、细胞浸润和促炎巨噬细胞活化得到改善。此外，将这些变化与在缓解期进行中性粒细胞耗竭时观察到的效应进行对比。在这种情况下，当中性粒细胞耗尽时，观察到消退机制受损，例如未能平衡促炎细胞因子和抗炎细胞因子比率，巨噬细胞表型转换为促恢复型的缺陷，以及修复和重塑过程缺陷。本研究描述了中性粒细胞作为小鼠中与饮食诱导的NASH相关的肝损伤和纤维化的触发剂和促消退介质的阶段依赖性对比作用。这些发现在设计NASH治疗策略时具有重要的翻译意义。
Inflammatory changes in the liver represent a key feature of non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD). Innate immune activation including hepatic neutrophilic infiltration acts as an important inflammatory trigger as well as a potential mediator of inflammation resolution. In this study, we dissected the effects of neutrophil depletion via anti-lymphocyte antigen 6 complex locus G6D (Ly6G) antibodies administration during ongoing high fat-fructose-cholesterol (FFC) diet-induced murine NASH and during inflammation resolution by switching into a low-fat control diet. During NASH progression, protective effects were shown as HSC activation, cell infiltration and activation of pro-inflammatory macrophages were ameliorated. Furthermore, these changes were contrasted with the effects observed when neutrophil depletion was performed during the resolution phase. Impaired resolving mechanisms, such as a failure to balance the pro and anti-inflammatory cytokines ratio, deficient macrophage phenotypic switch into a pro-restorative profile, and defective repair and remodeling processes were observed when neutrophils were depleted in this scenario. This study described phase-dependent contrasting roles of neutrophils as triggers and pro-resolutive mediators of liver injury and fibrosis associated with diet-induced NASH in mice. These findings have important translational implications at the time of designing NASH therapeutic strategies.
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影响因子：
8.9
作者：
Jennison E;Byrne CD
通讯作者：
Byrne CD
小鼠 Kupffer 细胞中硫氧还蛋白相互作用蛋白抑制 NLRP3 炎症小体作为非酒精性脂肪肝疾病发展的调节机制
影响因子：
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作者：
He K;Zhu X;Liu Y;Miao C;Wang T;Li P;Zhao L;Chen Y;Gong J;Cai C;Li J;Li S;Ruan XZ;Gong J
通讯作者：
Gong J
影响因子：
12.4
作者：
Calvente, Carolina Jimenez;Del Pilar, Hana;Feldstein, Ariel E.
通讯作者：
Feldstein, Ariel E.
影响因子：
4.6
作者：
Berkhout, Laura;Barikbin, Roja;Tiegs, Gisa
通讯作者：
Tiegs, Gisa
影响因子：
16.1
作者：
Higashi T;Friedman SL;Hoshida Y
通讯作者：
Hoshida Y