Objective: The immunosuppressive mechanism of sinomenine in organ allotransplantation was investigated, especially its effect of blocking dendritic cell (DC) maturation, which might influence the frequency of regulatory T cells (Tregs).
Methods: Bone marrow cells from male donor Wistar rats were induced to differentiate into DCs in vitro in the presence or absence of sinomenine, and characterized by flow cytometry. These two groups of DCs were respectively injected into male recipient Sprague-Dawley rats via the tail vein, at both high and low doses. Sprague-Dawley rats receiving saline injection were used as controls. Seven days later, renal transplantation was performed from donor Wistar rats to the recipient Sprague-Dawley rats. Seven days after transplantation, spleens were collected from the recipients. The proportions of Tregs and Foxp3+ Tregs to CD4+ T cells were determined using flow cytometry.
Results: With sinomenine treatment, the frequency of mature DCs was reduced, as indicated by lower expression of the surface markers CD80, CD86, and RT1B. In recipient Sprague-Dawley rats that received sinomenine-treated DCs before renal allotransplantation, the proportions of splenic Tregs and Foxp3+ Tregs were significantly higher than in control recipients receiving saline or DCs without sinomenine treatment (all p<0.05). A high dose of sinomenine-treated DCs (106 cells) had a more obvious effect in increasing Tregs than the low dose (105 cells) (p<0.05).
Conclusion: Pre-transplant infusion of donor-derived sinomenine-induced maturation arrested DCs could result in the increase of Foxp3+ Tregs in the spleens of recipients after renal allotransplantation.
Keywords: Dendritic cell; Immunosuppression; Regulatory T cell; Renal transplantation; Sinomenine.
Copyright © 2017. Published by Elsevier B.V.