衰老和肝脏免疫细胞。
Ageing and liver immune cells.
摘要(中文译文)
衰老与免疫系统失调有关，这导致老年人容易感染、恶性肿瘤、自身免疫性疾病和炎症性疾病。这种免疫功能障碍可分为两个过程：免疫反应性的逐渐下降（免疫衰老）和慢性低度全身炎症（炎症）。这些过程延续了一个循环，其中持续的炎症加速了免疫细胞的耗竭和衰老，而免疫监视的减弱加剧了炎症，共同促进了组织损伤和与年龄相关的疾病。肝脏是维持全身免疫耐受的关键免疫器官，随着与年龄相关的胸腺退化削弱了中枢耐受，肝脏在调节外周免疫耐受方面发挥着越来越重要的作用。衰老改变了肝脏的免疫环境，具有不同的浸润和结构重塑模式，其特征是出现与衰老相关的第三淋巴相关结构（ATLAS），富含局灶性炎性细胞簇。这些结构和相关的纤维化壁龛充当促炎和促纤维化信号传导的枢纽。转录组学研究显示，在整个老年肝脏中，炎症免疫途径和促炎细胞因子持续上调。免疫细胞失调，肝巨噬细胞向促炎表型转变，NK细胞疲劳，频率降低，衰老细胞清除受损。T细胞和B细胞分别随着衰老相关T细胞（SAT）和年龄相关B细胞（ABC）数量的增加而积累耗竭表型。肝窦内皮细胞（LSEC）经历假毛细血管化和去雌激素化，形成物理屏障，损害肝细胞清除邻近T细胞的组织。总之，肝脏免疫细胞中与年龄相关的免疫变化表明，肝脏在老年全身炎症中起着核心作用。
Abstract
Ageing is associated with a dysregulated immune system that contributes to vulnerability in older adults to infection, malignancies, autoimmune diseases, and inflammatory disorders. This immune dysfunction can be categorised into two processes: progressive decline in immune responsiveness (immunosenescence) and chronic low-grade systemic inflammation (inflammaging). These processes perpetuate a cycle wherein persistent inflammation accelerates immune cell exhaustion and senescence, while diminished immune surveillance heightens inflammation, together promoting tissue damage and age-related disease. The liver, a crucial immune organ pivotal for maintaining systemic immune tolerance, assumes an increasingly prominent role in regulating peripheral immune tolerance as age-related thymic involution diminishes central tolerance. Ageing alters the liver's immune landscape, with diverse patterns of infiltration and structural remodelling marked by the emergence of ageing-related tertiary lymphoid-associated structures (ATLAS), enriched with focal clusters of inflammatory cells. These structures and associated fibrotic niches function as hubs for pro-inflammatory and pro-fibrotic signalling. Transcriptomic studies reveal consistent upregulation of inflammatory immune pathways and pro-inflammatory cytokines across the aged liver. Immune cells are dysregulated with liver macrophages shifting toward pro-inflammatory phenotypes, NK cells showing exhaustion with reduction in frequency and impaired senescent cell clearance. T and B cells accumulate exhausted phenotypes with expanding populations of senescence-associated T cells (SATs) and age-associated B cells (ABCs), respectively. Liver sinusoidal endothelial cells (LSECs) undergo pseudo-capillarization and defenestration, creating a physical barrier that impairs clearance of tissue-adjacent T cells by hepatocytes. Taken together, age-related immune changes in liver immune cells indicate that the liver plays a central role in systemic inflammation in old age.
如何引用
AMA
Jarrod J Kennedy, Patrick Bertolino, Sophie Lucic Fisher, Meng C Ngu, Nicholas J Hunt, Peter A G McCourt, et al. Ageing and liver immune cells.. Ageing research reviews. 2026; doi:10.1016/j.arr.2026.103039.
APA
Jarrod J Kennedy, Patrick Bertolino, Sophie Lucic Fisher, Meng C Ngu, Nicholas J Hunt, Peter A G McCourt, et al (2026). Ageing and liver immune cells.. Ageing research reviews. https://doi.org/10.1016/j.arr.2026.103039
GB/T 7714
Jarrod J Kennedy, Patrick Bertolino, Sophie Lucic Fisher, Meng C Ngu, Nicholas J Hunt, Peter A G McCourt, et al. Ageing and liver immune cells.[J]. Ageing research reviews, 2026 doi:10.1016/j.arr.2026.103039.
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