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慢性肝损伤中的肝脏再生:聚焦于巨噬细胞和自然杀伤细胞的基础与临床应用。

Liver Regeneration in Chronic Liver Injuries: Basic and Clinical Applications Focusing on Macrophages and Natural Killer Cells.

机构信息

Central Laboratory, Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai, China.

出版信息

Cell Mol Gastroenterol Hepatol. 2022;14(5):971-981. doi: 10.1016/j.jcmgh.2022.05.014. Epub 2022 Jun 20.

Abstract

BACKGROUND & AIMS: Liver regeneration is a necessary but complex process involving multiple cell types besides hepatocytes. Mechanisms underlying liver regeneration after partial hepatectomy and acute liver injury have been well-described. However, in patients with chronic and severe liver injury, the remnant liver cannot completely restore the liver mass and function, thereby involving liver progenitor-like cells (LPLCs) and various immune cells.

RESULTS

Macrophages are beneficial to LPLCs proliferation and the differentiation of LPLCs to hepatocytes. Also, cells expressing natural killer (NK) cell markers have been studied in promoting both liver injury and liver regeneration. NK cells can promote LPLC-induced liver regeneration, but the excessive activation of hepatic NK cells may lead to high serum levels of interferon-γ, thus inhibiting liver regeneration.

CONCLUSIONS

This review summarizes the recent research on 2 important innate immune cells, macrophages and NK cells, in LPLC-induced liver regeneration and the mechanisms of liver regeneration during chronic liver injury, as well as the latest macrophage- and NK cell-based therapies for chronic liver injury. These novel findings can further help identify new treatments for chronic liver injury, saving patients from the pain of liver transplantations.

摘要

背景与目的

肝脏再生是一个必要但复杂的过程,除了肝细胞外,还涉及多种细胞类型。部分肝切除和急性肝损伤后的肝脏再生机制已经得到了很好的描述。然而,在慢性和严重肝损伤的患者中,残余肝脏不能完全恢复肝脏的质量和功能,从而涉及肝祖细胞样细胞(LPLCs)和各种免疫细胞。

结果

巨噬细胞有利于 LPLCs 的增殖,以及 LPLCs 向肝细胞的分化。此外,表达自然杀伤(NK)细胞标志物的细胞也被研究用于促进肝损伤和肝再生。NK 细胞可以促进 LPLC 诱导的肝再生,但是肝 NK 细胞的过度激活可能导致干扰素-γ的血清水平升高,从而抑制肝再生。

结论

本综述总结了最近关于 2 种重要的固有免疫细胞,巨噬细胞和 NK 细胞,在 LPLC 诱导的肝再生和慢性肝损伤期间肝再生的机制,以及基于巨噬细胞和 NK 细胞的慢性肝损伤的最新治疗方法。这些新发现可以进一步帮助确定慢性肝损伤的新治疗方法,使患者免受肝移植的痛苦。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09ed/9489753/ff431341742e/gr1.jpg

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