Pan Zheng, Ye Yan-Shuo, Liu Chang, Li Wei
Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
Hepatol Int. 2025 Apr;19(2):315-324. doi: 10.1007/s12072-025-10778-7. Epub 2025 Feb 1.
The tolerogenic immune microenvironment of the liver (the immune system avoids attacking harmless antigens, such as antigens derived from food and gut microbiota) has garnered significant attention in recent years. Inherent immune cells in the liver play a unique role in regulating this microenvironment. Liver-resident natural killer (LrNK) cells, also known as liver type 1 innate lymphoid cells (ILC1s), are a recently discovered subset of immune cells that possess properties distinct from those of conventional NK (cNK) cells. Accumulating evidence suggests that there are significant differences between LrNK and cNK cells, with LrNK cells potentially exhibiting immunosuppressive functions in the liver. This review summarizes the latest findings on LrNK cells, focusing on their phenotype, heterogeneity, plasticity, origin, development, and the required transcription factors. In addition, immune functions of LrNK cells in various liver diseases, including liver cancer, viral infections, liver injury, and cirrhosis, were analyzed. By elucidating the role of LrNK cells in liver immunity, this review aims to enhance our understanding of the mechanisms underlying liver immunity and contribute to the improvement of liver disease treatment.
肝脏的免疫耐受微环境（免疫系统避免攻击无害抗原，如源自食物和肠道微生物群的抗原）近年来受到了广泛关注。肝脏中的固有免疫细胞在调节这种微环境中发挥着独特作用。肝脏驻留自然杀伤（LrNK）细胞，也称为肝脏1型固有淋巴细胞（ILC1s），是最近发现的一类免疫细胞亚群，其特性与传统自然杀伤（cNK）细胞不同。越来越多的证据表明，LrNK细胞和cNK细胞之间存在显著差异，LrNK细胞可能在肝脏中发挥免疫抑制功能。本综述总结了关于LrNK细胞的最新研究结果，重点关注其表型、异质性、可塑性、起源、发育以及所需的转录因子。此外，还分析了LrNK细胞在各种肝脏疾病（包括肝癌、病毒感染、肝损伤和肝硬化）中的免疫功能。通过阐明LrNK细胞在肝脏免疫中的作用，本综述旨在增进我们对肝脏免疫机制的理解，并为改善肝脏疾病的治疗做出贡献。
