Document Type: Original Article
Transplant Research Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
Laboratory Animals Center, Shiraz University of Medical Sciences, Shiraz, Iran
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