AB0163 Mesenchymal stem cells induce CD1C+ tolerogenic dendritic cells in human systemic lupus erythematosus via up-regulating FLT-3 ligand

Abstract

BackgroundCD1c+ tolerogenic dendritic cells (DCs) play important roles in the induction of peripheral tolerance and control of adaptive immune response. Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) exhibit immunoregulation effects in systemic lupus erythematosus (SLE). However, the underlying immunosuppression mechanism of MSCs via tolerogenic DCs in SLE remains largely unknown.ObjectivesThe aim of this study was to examine tolerogenic DCs levels in SLE patients, and to further investigate the mechanism of MSCs in the regulation of tolerogenic DCs.MethodsTolerogenic DCs were isolated as Lin (CD3/19/56/14)- HLA DR+CD11c+CD1c+ from peripheral blood mononuclear cells (PBMCs). Levels of tolerogenic DCs were determined by flow cytometry, and serum concentration of Flt-3 ligand (FLT3L) were determined by ELISA from 17 healthy controls and 25 SLE patients. Eight SLE patients were given UC MSCs infusions. We compared the levels of tolerogenic DCs and serum FLT3L before and 24 hours after UC MSCs transplantation. PBMCs from 8 patients were collected and co-cultured with UC MSCs at ratios of 1:1, 10:1 and 50:1, for 24 hours, 48 hours and 72 hours, respectively, to detect the levels of tolerogenic DCs. The FLT3L in the supernatant solution were determined. FLT3L siRNA was added to the co-culture system, and the level of tolerogenic DCs were detected.ResultsThe levels of peripheral CD1c+ DCs and serum FLT3L were significantly decreased in SLE patients compared to healthy controls. After UC MSCs transplantation, the levels of CD1c+ DCs increased, along with an increase in serum FLT3L. In vitro studies showed that UC MSCs time-dependently up-regulated peripheral CD1c+ DCs, but not dose-dependently. The supernatant FLT3L level significantly increased after co-cultured with MSCs. However, the addition of FLT3L siRNA significantly abrogated the up-regulation of CD1c+ DCs by MSCs.ConclusionsUC MSCs induce CD1c+ tolerogenic DCs through up-regulating FLT3L in lupus patients.Disclosure of InterestNone declared