脾脏
运动性
病理
CX3CR1型
肝纤维化
活体显微镜检查
纤维化
医学
化学
炎症
细胞生物学
免疫学
生物
内科学
趋化因子
微循环
趋化因子受体
作者
Chuntan Han,Yujie Zhai,Yuke Wang,Xuwen Peng,Xian Zhang,Bolei Dai,Yuehong Leng,Zhihong Zhang,Shuhong Qi
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2024-01-01
卷期号:14 (5): 2210-2231
摘要
CX3CR1 + cells play a crucial role in liver fibrosis progression.However, changes in the migratory behavior and spatial distribution of spleen-derived and hepatic CX3CR1 + cells in the fibrotic liver as well as their influence on the liver fibrosis remain unclear. Methods:The CX3CR1 GFP/+ transgenic mice and CX3CR1-KikGR transgenic mice were used to establish the CCl4-induced liver fibrosis model.Splenectomy, adoptive transfusion of splenocytes, in vivo photoconversion of splenic CX3CR1 + cells and intravital imaging were performed to study the spatial distribution, migration and movement behavior, and regulatory function of CX3CR1 + cells in liver fibrosis. Results:Intravital imaging revealed that the CX3CR1 GFP cells accumulated into the fibrotic liver and tended to accumulate towards the central vein (CV) in the hepatic lobules.Two subtypes of hepatic CX3CR1 + cells existed in the fibrotic liver.The first subtype was the interacting CX3CR1 GFP cells, most of which were observed to distribute in the liver parenchyma and had a higher process velocity; the second subtype was mobile CX3CR1 GFP cells, most of which were present in the hepatic vessels with a faster moving speed.Splenectomy ameliorated liver fibrosis and decreased the number of CX3CR1 + cells in the fibrotic liver.Moreover, splenectomy rearranged CX3CR1 GFP cells to the boundary of the hepatic lobule, reduced the process velocity of interacting CX3CR1 GFP cells and decreased the number and mobility of mobile CX3CR1 GFP cells in the fibrotic liver.Transfusion of spleen-derived classical monocytes increased the process velocity and mobility of hepatic endogenous CX3CR1 GFP cells and facilitated liver fibrosis progression via the production of proinflammatory and profibrotic cytokines.The photoconverted splenic CX3CR1 + KikRed + cells were observed to leave the spleen, accumulate into the fibrotic liver and contact with hepatic CX3CR1 + KikGreen + cells during hepatic fibrosis. Conclusion:The splenic CX3CR1 + monocytes with classical phenotype migrated from the spleen to the fibrotic liver, modifying the migratory behavior of hepatic endogenous CX3CR1 GFP cells and exacerbating liver fibrosis via the secretion of cytokines.This study reveals that splenic CX3CR1 + classical monocytes are a key driver of liver fibrosis via the spleen-liver axis and may be potential candidate targets for the treatment of chronic liver fibrosis.
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