SLPI-Loaded Liposomes Targeting Kupffer Cells Modulate Macrophage Polarization and Mitigate Radiation-Induced Liver...

Area of Science:

• Immunology
• Hepatology
• Radiation Oncology

Background:

• Kupffer cells (KCs) are crucial liver immune sentinels.
• Their role in radiation-induced liver damage (RILD) is not well understood.

Purpose of the Study:

• Investigate KC functional and phenotypic changes in RILD.
• Identify therapeutic targets for mitigating RILD.

Main Methods:

• Established a mouse model of RILD.
• Performed single-cell profiling of hepatic immune cells.
• Utilized KC depletion/reconstitution and molecular assays.

Main Results:

• Radiation induces a pro-inflammatory M1 phenotype shift in KCs.
• M1-polarized KCs exacerbate liver damage via secretory leukocyte protease inhibitor (SLPI).
• Liposomal SLPI inhibition in KCs suppressed M1 polarization and alleviated RILD.

Conclusions:

• Radiation promotes an SLPI-dependent pro-inflammatory M1 state in KCs, worsening liver injury.
• Targeted SLPI suppression offers a promising therapeutic approach for RILD.