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Interleukin-10 and Transforming Growth Factor-β Cytokines Decrease Immune Activation During Normothermic Ex Vivo
Kristin N Carlson1, Juliana Pavan-Guimaraes, Joshua C Verhagen
1Division of TransplantationDepartment of Surgery University of Wisconsin School of Medicine and Public Health Madison WI Department of Pathology and Laboratory Medicine University of Wisconsin School of Medicine and Public Health Madison WI Department of PediatricsCarbone Cancer Center University of Wisconsin School of Medicine and Public Health Madison WI Carbone Cancer Center University of Wisconsin School of Medicine and Public Health Madison WI.
Normothermic ex vivo liver perfusion (NEVLP) activates liver immune cells. Adding interleukin 10 (IL10) and transforming growth factor β (TGF-β) reduced this activation and improved liver function, showing therapeutic potential for organ preservation.
Area of Science:
- Immunology
- Transplantation Biology
- Organ Preservation
Background:
- Normothermic ex vivo liver perfusion (NEVLP) is a promising organ preservation technique.
- Limited understanding exists regarding NEVLP's impact on liver-resident immune cell activation.
- Inflammatory responses during NEVLP require further investigation.
Purpose of the Study:
- To investigate the effects of NEVLP on liver-resident immune cell activation.
- To assess the efficacy of interleukin 10 (IL10) and transforming growth factor β (TGF-β) in mitigating immune activation and improving organ function during NEVLP.
- To evaluate NEVLP's impact on liver damage and cellular apoptosis.
Main Methods:
- Rat livers underwent NEVLP for 4 hours at 37°C, with or without IL10 and TGF-β.
- Control groups included naïve livers and livers preserved via static cold storage.
- Analyses included single-cell RNA sequencing, flow cytometry for immune cell activation markers (MHC II, CD40, CD86), and ELISA for cytokine production.
Main Results:
- NEVLP induced a pro-inflammatory gene expression profile in liver macrophages and dendritic cells.
- Increased cell-surface expression of MHC II, CD40, and CD86 was observed on immune cells post-NEVLP.
- IL10 and TGF-β partially reduced immune activation markers but did not alter cytokine production.
- Liver damage and apoptosis were minimal; IL10 and TGF-β treatment improved liver function.
Conclusions:
- NEVLP activates liver-resident immune cells at both gene and protein levels.
- Therapeutic intervention with IL10 and TGF-β can ameliorate NEVLP-induced immune activation.
- NEVLP with IL10 and TGF-β shows potential for improved organ preservation and function prior to transplantation.
