BACKGROUND: The immunoregulatory properties of mesenchymal stem cells (MSCs) have been well characterized in vitro. However, the role of MSCs in organ transplantation remains unclear. The purpose of this study was to examine the role of @entity3035 2, 3-dioxgenase (IDO)-transfected MSCs in immunoregulation both in vitro and in vivo. METHODS: Wild-type (WT) MSCs, empty lentivirus-transfected MSCs (Lenti-MSCs) or IDO-lentivirus-transfected MSCs (IDO-MSCs) were cocultured with peripheral blood mononuclear cells (PBMCs) or CD4CD25 regulatory T (Treg) cells to examine the impact of IDO on the immunoregulatory properties of MSCs in vitro. @entity361 , Lenti-MSCs or IDO-MSCs (2 * 10/kg) were intravenously injected into @entity95 renal transplant recipients immediately after surgery to examine the role of IDO-MSCs in tolerance induction in vivo. RESULTS: @entity45301 resulted in stable expression of IDO. The IDO-MSCs inhibited the proliferation of CD4CD25 effector T cells to a greater extent than @entity361 . Coculture of PBMCs and IDO-MSCs induced a higher percentage of CD4CD25Foxp3 Treg cells in PBMCs. Additionally, the antigen-specific suppressive function of these CD4CD25 Treg cells was increased. The IDO-MSCs-treated Treg cells showed upregulated expression of @entity68098 and increased secretion of @entity17662 and TGF-b. Low doses of IDO-MSCs prolonged graft survival and induced tolerance by inducing antigen-specific CD4CD25 Treg cells, as evidenced by the finding that IDO-MSCs-treated kidney transplant recipients accepted donor-specific skin grafts but rejected third-party grafts. CONCLUSIONS: The IDO increased the direct immunoregulatory properties of MSCs. The IDO-MSCs enhanced the expression and function of CD4CD25 Foxp3 Treg cells and induced allograft tolerance.

XXXX 2, 3-Dioxgenase Transfected Mesenchymal Stem Cells Induce Kidney Allograft Tolerance by Increasing the Production and Function of Regulatory T Cells.

@entity3035 :: ('CHEBI:28626', 'Chemical') :: ['indoleamine'] @entity45301 :: ('MESH:D016180', 'Disease') :: ['Lentivirus infection of MSCs'] @entity95 :: ('9986', 'Species') :: ['rabbit'] @entity17662 :: ('100008701(Tax:9986)', 'Gene') :: ['IL-10'] @entity68098 :: ('100009412(Tax:9986)', 'Gene') :: ['cytotoxic T-lymphocyte-associated antigen 4'] @entity361 :: ('MESH:C535700', 'Disease') :: ['WT-MSCs']
@entity3035 :: (CHEBI:28626,Chemical) :: ['Indoleamine']
