Ageing and liver immune cells.

Jarrod J Kennedy, Patrick Bertolino, Sophie Lucic Fisher, Meng C Ngu, Nicholas J Hunt, Peter A G McCourt, Victoria C Cogger, David G Le Couteur

School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia; ANZAC Research Institute, Concord Hospital, Sydney Local Health District, Concord, Australia. Electronic address: [email protected] of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, Australia; ANZAC Research Institute, Concord Hospital, Sydney Local Health District, Concord, Australia. Electronic address: [email protected]. · pubmed

Paper

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.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

Age-related immune changes in liver immune cells contribute to systemic inflammation in old age. The paper addresses the underlying mechanisms of immune dysfunction in aging, which is crucial for understanding and potentially mitigating age-related diseases.

Author of this paper? Send a correction.