Prolongation of cardiac allograft survival in mice by Decitabine-induced upregulation of Foxp3 expression
10.3760/cma.j.issn.0254-1785.2013.06.012
- VernacularTitle:地西他滨诱导体内Foxp3基因表达上调延长心脏移植小鼠的存活时间
- Author:
Hao GUO
;
Xianghui HE
;
Liwui ZHU
- Publication Type:Journal Article
- Keywords:
Mice;
Heart transplantation;
CD4+ CD25+ T-Lymphocytes;
Foxp3
- From:
Chinese Journal of Organ Transplantation
2013;(6):370-373
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Foxp3 gene expression induced with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (Aza) in recipients on ameliorating allograft rejection and prolonging allograft survival and the possible mechanisms.Method BALB/c and C57BL/6 splenocytes treated with mitomycin (MMC) served as the stimulators,those not treated with MMC as responders,and they were subjected to one-way mixed lymphocyte culture (MLC).In the presence or absence of Aza,the percentage of CD4+ CD25+ Tregs was detected by flow cytometry.Abdominal heterotopic heart transplantation model was established by using inbred male Balb/c mice as donors and C57BL/6 as recipients respectively.In experimental group,recipients were intravenously administrated with decitabine (1.5 mg/kg/day) on the day 1 to day 3 post-transplantation.The control mice were treated with normal saline.CD4+ CD25+ Tregs proportion in the blood and Foxp3 mRNA in cardiac grafts and spleen of recipients were measured respectively,and the survival and the histopathologic changes of the cardiac grafts were also observed.Result Decitabine enhanced the proliferation CD4 + CD25 + Tregs of MLC in vitro.The median survival time of the cardiac grafts in experimental group (11 days) was longer than that in control group (7 days) (P＜0.01).As compared with control group,Foxp3 mRNA expression in the cardiac grafts and spleen in recipient mice was significantly up-regulated,and CD4+ CD25 + Tregs proportion was increased (P＜0.01) and the proliferation of lymphocytes and monocytes infiltration was inhibited.Conclusion Up-regulation of Foxp3 gene expression induced with decitabine in recipients could alleviate cardiac allograft rejection and prolong cardiac allograft survival via the induction of proliferation and differentiation of CD4+ CD25 + Foxp3 + Tregs.
