A critical role of TRAIL expressed on cotransplanted hepatic stellate cells in prevention of islet allograft rejection

Hepatic stellate cells (HSCs) have demonstrated a strong T‐cell inhibitory activity. In a mouse islet transplantation model, cotransplanted HSCs can protect islet allografts from rejection. The involved mechanism is not fully understood. We showed in this study that expression of tumor necrosis fact...

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Bibliographic Details
Published in:Microsurgery 2010-05, Vol.30 (4), p.332-337
Main Authors: Yang, Horng-Ren, Hsieh, Ching-Chuan, Wang, Lianfu, Fung, John J., Lu, Lina, Qian, Shiguang
Format: Article
Language:English
Subjects:
Animals
Biomarkers - metabolism
Cell Proliferation
Cell Transplantation - adverse effects
Cell Transplantation - methods
Dendritic Cells - transplantation
Diabetes Mellitus, Experimental - surgery
Disease Models, Animal
Flow Cytometry
Graft Rejection - prevention & control
Graft Survival
Hepatic Stellate Cells - metabolism
Hepatic Stellate Cells - transplantation
Islets of Langerhans Transplantation - adverse effects
Islets of Langerhans Transplantation - methods
Kaplan-Meier Estimate
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Random Allocation
Reverse Transcriptase Polymerase Chain Reaction
TNF-Related Apoptosis-Inducing Ligand - genetics
TNF-Related Apoptosis-Inducing Ligand - metabolism
Transplantation, Homologous
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Summary:Hepatic stellate cells (HSCs) have demonstrated a strong T‐cell inhibitory activity. In a mouse islet transplantation model, cotransplanted HSCs can protect islet allografts from rejection. The involved mechanism is not fully understood. We showed in this study that expression of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), an important apoptosis‐inducing ligand, on HSCs was crucial in protection of islet allografts, since HSCs derived from TRAIL knockout mice demonstrated less inhibitory activity towards T‐cell proliferative responses, and substantially lost their capacity in protecting cotransplanted islet allografts from rejection, suggesting that TRAIL‐mediated T cell apoptotic death is important in HSC‐delivered immune regulation activity. © 2009 Wiley‐Liss, Inc. Microsurgery 2010.
ISSN:0738-1085
1098-2752
DOI:10.1002/micr.20697