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 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.
Yang
Horng-Ren
HR
Department of General Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
Hsieh
Ching-Chuan
CC
Wang
Lianfu
L
Fung
John J
JJ
Lu
Lina
L
Qian
Shiguang
S
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D017690:Cell Transplantation / Q000009:adverse effects / Q000379:methods; D003713:Dendritic Cells / Q000637:transplantation; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000637:transplantation*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects* / Q000379:methods; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D014184:Transplantation, Homologous
D015415:Biomarkers; D053221:TNF-Related Apoptosis-Inducing Ligand