Role of toll-like receptor signaling in skin transplantation responses in mice / 中华器官移植杂志

ABSTRACT

Objective To investigate the essential role of Toll-like receptor (TLR) signaling in dendritic cells in rejection responses of skin transplantation in mice.Method Immature wild-type BALB/c bone marrow dentritic cells (BMDCs) were stimulated by a TLR agonist,CpG,in the presence of ST2825,an inhibitor of key molecule myeloid differentiation factor 88 (MyD88) in TLR signal transduction,or in the absence for 24 h in vitro.Co-stimulatory molecules CD80 and CD86 were analyzed by flow cytometry.Wild-type C57BL/6 na ve T cells stained with CFSE,a fluorescent dye,were co-cultured with BALB/c DCs for 3 days in the presence or absence of ST2825.CD3 +/CFSE+cells were analyzed by flow cytometry.Minor antigen-mismatched (HY-mismatched) skin allograft model was employed in this study in which the donors were all males and the recipients were all females.The experimental groups were divided as followsthe control group,the donors and the recipients were all wide type BALB/c mice; the MyD88 group,the donors and the recipients were all MyD88-konckout BALB/c mice; the DCs group,the donors and the recipients were all MyD88-knockout BALB/c mice and the recipients were transfused with donor-sourced DCs after transplantation; the experimental group,the donors and the recipients were all MyD88-knockout BALB/c mice and the recipients were transfused with donor-sourced DCs pre-treated with ST2825after transplantation.The survival time of skin allografts was observed.Result ST2825 could dose dependently inhibit the high level expression of co-stimulatory molecules CD80 and CD86 induced with CpG.Similarly,and it could also dosedependently inhibit the allo-reactive T cell proliferation upon the stimulation with DCs.The survival time of every group was as followsthe control group (22.8 ±2.8) days vs.the MyD88 group (＞100 days) vs.the DCs group (9.7± 2) days vs.the experimental group (＞100 days,P＜0.05,vs.the DC group).Conclusion DCs may play an essential role in rejection responses of transplantation via TLR signaling.The inhibitor of TLR signaling,ST2825,could inhibit the activation of DCs and the biological functions,which might be contributed to the inhibitory effects of ST2825 on DCs maturation and indirect suppression on the proliferation of allo reactive T cells.