Liver infiltration of multiple immune cells during the process of acute liver injury and repair.

Liver infiltration of multiple immune cells during the process of acute liver injury and repair.
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DOI:
10.3748/wjg.v28.i46.6537
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发表时间:
2022-12-14
影响因子:
4.3
通讯作者:
Gao Y
Gao Y
中科院分区:
医学2区
文献类型:
--
作者:
Xie Y;Zhong KB;Hu Y;Xi YL;Guan SX;Xu M;Lin Y;Liu FY;Zhou WJ;Gao Y

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免疫细胞,包括中性粒细胞、自然杀伤(NK)细胞、T细胞、NKT细胞和巨噬细胞,参与急性肝损伤的进展和肝恢复。到目前为止,还没有系统的研究这些不同的免疫细胞从最初的损伤到随后的恢复的定量变化。 观察急性肝损伤模型中不同免疫细胞浸润随时间的变化,探讨白细胞源性趋化因子2(LECT 2)的变化与多种免疫细胞浸润的关系。四氯化碳和刀豆球蛋白A诱导的急性肝损伤模型分别模拟毒素诱导的和自身免疫介导的肝损伤。在不同时间点监测各种免疫细胞的定量变化。收集血清样品,并收获肝组织。Ly 6 G、CD 161、CD 4、CD 8和F4/80染色分别用于指示中性粒细胞、NK/NKT细胞、CD 4 + T细胞、CD 8 + T细胞和巨噬细胞。Lect 2-KO小鼠用于检测LECT 2的功能。 在损伤和修复过程中,不同类型的免疫细胞开始增加,在不同的时间点达到高峰并陷入衰退。血清谷丙转氨酶(ALT)和谷草转氨酶(AST)指标在伤后7 d恢复正常,但免疫细胞浸润在伤后14 d仍存在,表现出明显的滞后效应。我们发现,在急性肝损伤小鼠模型中,LECT 2的表达上调,并且Lect 2-KO小鼠的肝损伤比野生型小鼠轻。与野生型小鼠相比,Lect 2-KO小鼠具有不同的免疫细胞浸润。在肝脏修复过程中,免疫细胞的恢复时间远远落后于血清ALT和AST。LECT 2可调节单核/巨噬细胞的趋化性,可能成为急性肝损伤的治疗靶点。
Immune cells, including neutrophils, natural killer (NK) cells, T cells, NKT cells and macrophages, participate in the progression of acute liver injury and hepatic recovery. To date, there has been no systematic study on the quantitative changes in these different immune cells from initial injury to subsequent recovery. To investigate the infiltration changes of various immune cells in acute liver injury models over time, and to study the relationship between the changes in leukocyte cell-derived chemotaxin 2 (LECT2) and the infiltration of several immune cells. Carbon tetrachloride- and concanavalin A-induced acute liver injury models were employed to mimic toxin-induced and autoimmune-mediated liver injury respectively. The quantitative changes in various immune cells were monitored at different time points. Serum samples were collected, and liver tissues were harvested. Ly6G, CD161, CD4, CD8 and F4/80 staining were used to indicate neutrophils, NK/NKT cells, CD4+ T cells, CD8+ T cells and macrophages, respectively. Lect2-KO mice were used to detect the function of LECT2. During the injury and repair process, different types of immune cells began to increase, reached their peaks and fell into decline at different time points. Furthermore, when the serum alanine transaminase (ALT) and aspartate transaminase (AST) indices reverted to normal levels 7 d after the injury, the infiltration of immune cells still existed even 14 d after the injury, showing an obvious lag effect. We found that the expression of LECT2 was upregulated in acute liver injury mouse models, and the liver injuries of Lect2-KO mice were less severe than those of wild-type mice. Compared with wild-type mice, Lect2-KO mice had different immune cell infiltration. The recovery time of immune cells was far behind that of serum ALT and AST during the process of liver repair. LECT2 could regulate monocyte/macrophage chemotaxis and might be used as a therapeutic target for acute liver injury.
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