Senescent Human Liver Endothelial Cells Mediate CD4⁺ T Cell Recruitment via ICOSL

Area of Science:

• Cellular senescence
• Liver disease pathology
• Immunology

Background:

• Senescent cells are implicated in chronic liver disease, but their role in liver endothelial cells is understudied.
• Previous research focused on epithelial cell senescence, leaving endothelial cell senescence largely unexplored.

Purpose of the Study:

• To investigate the presence and function of senescent liver endothelial cells in chronic liver disease.
• To explore the role of inducible T cell costimulator ligand (ICOSL) in senescent liver endothelial cell-mediated immune responses.

Main Methods:

• Analysis of single-cell RNA-sequencing data and immunohistochemistry.
• Induction of paracrine senescence in primary human liver endothelial cells.
• In vitro functional assays under physiological flow conditions.

Main Results:

• Senescent liver endothelial cells show reduced scavenging capacity but support lymphocyte recruitment.
• ICOSL is crucial for CD4+ T cell recruitment, but not CD8+ T cell recruitment.
• ICOSL is upregulated in diseased liver tissues and correlates with CD4+ T cell infiltration.

Conclusions:

• Senescent human liver endothelial cells can influence the liver immune microenvironment in chronic liver disease.
• Targeting senescent endothelial cells presents a potential therapeutic avenue for chronic liver diseases.