Document Type : Original Article


1 Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

2 Laboratory Animals Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz,


Background: 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.
Objectives: 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. Methods: 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. Results: 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 Tcells.
But, we could not find any differences in ILT3 expression between MSC-treated
DCs and untreated ones. Conclusion: 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 upregulation
of ILT3.