Project Details
Abstract
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:PC10108-0912
External Project ID:NSC101-2320-B182-037-MY3
External Project ID:NSC101-2320-B182-037-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/12 → 31/07/13 |
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