Interaction between liver sinusoidal endothelial cells and hepatocytes through the IL-1α–IL1R1 pathway worsens ischaemia/reperfusion injury in older livers

By
Yasong Liu
Tingting Wang
Feng Zhang
Xuying Liu
Zhongying Hu
Jiebin Zhang
Haitian Chen
Jiaqi Xiao
Qiang You
Zhengqi Wu
Jia Yao
Yingcai Zhang
Shuhong Yi
Hua Li
Qi Zhang
Yang Yang
Rong Li
Jun Zheng
August 1, 2026

Overview

This study identifies the IL-1α–IL1R1 signaling pathway as a critical mediator of exacerbated ischaemia/reperfusion injury (IRI) in aged livers.

Background

Ischaemia-reperfusion injury (IRI) significantly complicates liver surgeries, particularly in older patients who are more susceptible to such injuries. Understanding the cellular interactions that exacerbate IRI in aged livers is crucial for improving surgical outcomes and developing targeted therapies. This study focuses on the role of liver sinusoidal endothelial cells (LSECs) and their interaction with hepatocytes in the context of aging and IRI.

Data Highlights

No numerical data or trial data presented in the source material.

Key Findings

Hepatocyte-directed signaling from LSECs increases with liver aging.
Senescent LSECs show elevated MEIS2 transcriptional activity, leading to increased IL-1α expression.
IL-1α activates the IL1R1-NF-κB signaling pathway in hepatocytes, promoting inflammation.
Hepatocyte-derived TNF-α enhances MEIS2 activity in LSECs, creating a proinflammatory feedback loop.
Blockade of the IL-1α–IL1R1 axis significantly reduces hepatic injury in aged rat liver transplantation models.

Clinical Implications

The study identifies the IL-1α–IL1R1 signaling pathway as a key driver of exacerbated IRI in aged livers.

Conclusion

The study highlights the role of LSEC and hepatocyte interactions in exacerbating IRI in aged livers.

Interaction between liver sinusoidal endothelial cells and hepatocytes through the IL-1α–IL1R1 pathway worsens ischaemia/reperfusion injury in older livers