Effect of CD40 silenced dendritic cells by RNA interference on mice skin allograft rejection
Effect of CD40 silenced dendritic cells by RNA interference on mice skin allograft rejection
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DOI：
10.2217/imt.14.112
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发表时间：
2015-01-01
期刊：
影响因子：
2.8
通讯作者：
Ebrahimnezhad, Salimeh
中科院分区：
文献类型：
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作者：
Karimi, Mohammad Hossein;Marzban, Saeed;Ebrahimnezhad, Salimeh
目的：致耐受性树突状细胞（DC）在诱导和维持免疫耐受中起重要作用。CD 40是肿瘤坏死因子受体超家族成员，是一种有效的T细胞共刺激分子。因此，本研究旨在探讨RNA干扰沉默CD 40的DC对小鼠皮肤移植排斥反应的影响。材料与方法：采用C57 BL/6小鼠皮肤移植于BALB/c小鼠。皮肤移植受者被分为四组（n = 5）。在移植前7天静脉注射CD 40下调的DC至BALB/c小鼠。比较各组移植物存活时间、Treg生成、CD 4+和CD 8 + T细胞浸润及血清细胞因子水平。结果如下：与未处理组相比，转染CD 40 siRNA的DC可显著延长移植物存活时间，增加Treg细胞、IL-4和IL-10水平，减少移植物内CD 4+和CD 8 + T细胞数量。IFN-γ和IL-12分泌也减少。结论：综上所述，这些数据表明，下调DC中的CD 40可以扩增Treg细胞并增加皮肤移植物存活。
Aim: Tolerogenic dendritic cells (DCs) play a critical role in inducing and maintaining tolerance. CD40 is a member of tumor necrosis factor receptor super family and is a potent T-cell costimulatory molecule. Therefore, in this study we evaluated the effect of CD40 silenced DCs by RNA interference on mice skin allograft rejection. Materials & methods: Skin transplantation was performed from C57BL/6 to BALB/c mouse. Skin allograft recipients were assigned to four groups (n = 5). CD40 downregulated DCs were injected to the BALB/c mice intravenously 7 days before transplantation. Then, graft survival time, Treg generation, CD4(+) and CD8(+) T cells infiltration and cytokine levels in serum of this group were compared with those of untreated and cyclosporine groups. Results: In comparison with untreated group, BALB/c mice injected with CD40 siRNA transfected DCs showed an increased graft survival time, Treg cells, IL-4 and IL-10 cytokine levels as well as decreased number of intragraft CD4(+) and CD8(+) T cells. IFN- and IL-12 secretion were diminished, too. Conclusion: Taken together, these data demonstrate that downregulation of CD40 in DCs can expand Treg cells and increase skin allograft survival.