Soluble CD83 inhibits acute rejection by up regulating TGF-β and IDO secretion in rat liver transplantation.

BACKGROUND:Allogeneic transplantation immune tolerance is currently a hot research issue and soluble CD83(sCD83) is a novel immunomodulator with great potential in inducing transplantation tolerance. OBJECTIVE:To investigate the mechanism of the immune tolerance effect of sCD83 on rat liver transplantation. METHOD:A rat liver transplantation model was established to study the effects of sCD83 on the expression levels of IL-2, IL-10, and TGF-β in peripheral blood and the mRNA expressions of foxp3, TGF-β, and Indoleamine 2,3-dioxygenase (IDO) in liver. The expression changes of costimulatory molecules CD80, CD86, and MHC-II on the surface of DC cells and the expressions of IDO + DC cell, TGF-β + CD4 + T cell, and CD4 + CD25 + Foxp3 + T cell were analyzed and compared. RESULTS:sCD83 alleviated the rejection activity index (RAI) of rat liver transplantation in the early stage, increased the expressions of TGF-β, IL-10 in peripheral blood and the mRNAs of IDO, TGF-β and foxp3 in the transplanted liver, and down-regulated the expressions of MHC-II, CD86, and CD80 in DC cells, resulting in significant increased numbers of tolerogenic TGF-β + CD4 + T cells, Treg cells, and IDO + DC cells with low expression. CONCLUSION:sCD83 inhibited acute rejection after liver transplantation in an allogeneic rat, and the mechanism was associated with the effect that sCD83 increased the expression of TGF-β, activated IDO immunosuppressive pathway, and increased tolerogenic DC cells and Treg cells.