Effect of Mesenchymal Stem Cells on ILT3 Expression in the Splenocytes of Skin Graft Recipient Mice.

Abstract

Mesenchymal stem cells (MSCs) are considered as effective therapeutic cells in transplantation due to their immunomodulatory activities. However, precise mechanism of MSCs immunomodulatory activity is not completely understood. To study the role of Immunoglobulin-like transcripts-3 (ILT3) immunomodulatory receptor in immune tolerance induced by MSCs in skin transplantation model and induction of tolerogenic dendritic cells (Tol-DCs) by MSCs through up-regulation of ILT3. C57BL/6 skin grafts were transplanted to the back of BALB/c mice. Recipient mice received MSCs on days 0, 1 and 2 post transplantation. On days 2, 5 and 10 post skin transplantation, ILT3 and forkhead box P3 (FOXP3) expression in the spleens of MSCs treated mice were evaluated. Furthermore, MSCs and DCs were co-cultured in cell culture plates and transwell systems. Then, the expressions of ILT3 mRNA and protein in MSC-treated DCs were evaluated. Additionally, MSC-treated DCs were co-cultured with allogeneic T-cells and FOXP3 expression in T-cells was evaluated. The expression of ILT3 and FOXP3 were higher in the splenocytes of MSCs-treated mice early post-transplantation. Furthermore, we observed that MSC-treated DCs can increase FOXP3 expression in T-cells. But, we could not find any differences in ILT3 expression between MSC-treated DCs and untreated ones. One of the mechanisms underlying MSCs immunomodulatory function could be up-regulating ILT3 expression in splenocytes. But our results did not support the hypothesis that MSCs induce Tolergenic DCs by up-regulation of ILT3.