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

Microsurgery. 2010 May;30(4):332-7. doi: 10.1002/micr.20697.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • 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

Substances

  • Biomarkers
  • TNF-Related Apoptosis-Inducing Ligand