Immunological and Regenerative Aspects of Hepatic Mast Cells in Liver Allograft Rejection and Tolerance

  • Nakano, Toshiaki (PI)
  • Chen, Chao-Long (CoPI)
  • Cheng, Yu-Fan (CoPI)
  • Goto, Shigeru (CoPI)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


In certain class I and class II disparate rat strain combinations such as DA (MHC haplotype RT1a) donor and PVG recipient (RT1c), orthotopic liver transplantation (OLT) results in a state of long-lasting and donor specific tolerance without pharmacological immunosuppression, whereas skin, heart and renal allografts undergo acute rejection (Kamada N, et al. Nature 1981). However, the molecular and cellular basis of rejection and liver transplant tolerogenicity is still poorly understood. In our pilot study, we confirmed the induction of stem cell factor (SCF) and its receptor c-Kit, which are critical to the migration and development of not only stem cells but also mast cells, in the tolerogenic livers as compared with rejective livers. The significant elevation of mast cell tryptase and high-affinity IgE receptor in the tolerogenic livers suggested the activation of mast cells in liver allografts at the tolerogenic phase after OLT. It has recently been reported that mast cells may be instrumental in orchestrating regulatory T cell (Treg)-mediated peripheral tolerance, while some groups reported that mast cells were strongly correlated with acute and chronic liver allograft rejection. Therefore, the precise roles of mast cells in liver allograft rejection and tolerance are still unknown. We also confirmed the replacement of hepatic cells from donor to the recipient, suggesting the significance of migration and differentiation of bone marrow−derived stem cells into hepatic stem/progenitor cells in tolerogenic livers after OLT. In this project, we will first explore the localization and interaction of hepatic mast cells and Tregs in liver allografts, and evaluate the significance of migration and differentiation of bone marrow−derived stem cells into hepatic cells in a rat tolerogenic OLT model (1st year). We will next clarify the immunological and regenerative aspects of hepatic mast cells for induction and maintenance of immune tolerance and liver regeneration in vitro (2nd year). Finally, we will discuss the therapeutic potential of mast cell-mediated immune regulation and liver regeneration in the inflamed and rejective livers in vivo (3rd year).

Project IDs

Project ID:PC10202-0564
External Project ID:NSC101-2320-B182-037-MY3
Effective start/end date01/08/1331/07/14


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