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

Objective:

To elucidate the cellular contributors and mechanisms exacerbating ischaemia-reperfusion injury (IRI) in aged livers.

Approach:

Single-cell transcriptomics: Utilized scRNA-seq and spatial transcriptomics to analyze liver samples from young and aged rats and humans.

Key Findings:

Hepatocyte-directed signaling from liver sinusoidal endothelial cells (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 and worsening hepatic IRI.
Hepatocyte-derived TNF-α enhances MEIS2 activity in LSECs, creating a proinflammatory feedback loop.
Blockade of the IL-1α–IL1R1 axis reduces hepatic injury in aged rat liver transplantation models.

Interpretation:

The study identifies the IL-1α–IL1R1-mediated interaction between LSECs and hepatocytes as a significant factor in exacerbating IRI in aged livers, suggesting a potential therapeutic target.

Limitations:

The study primarily focuses on animal models, which may not fully replicate human responses.

Conclusion:

Targeting the IL-1α–IL1R1 pathway may enhance hepatic resilience to surgical stress in elderly patients.

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

Objective:

Approach:

Key Findings:

Interpretation:

Limitations:

Conclusion:

Original Source(s)

Crosstalk between liver sinusoidal endothelial cells and hepatocytes via IL-1α–IL1R1 axis exacerbates ischaemia/reperfusion injury in aged livers

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