Introduction: The ability of dendritic cells (DCs) to initiate an immune response or induce immune tolerance depends on their maturation status. Dendritic-cell-associated C-type lectin 1 (Dectin-1) plays a key role in the differentiation, activation, and maturation of DCs. Therefore, we hypothesized that inhibition of Dectin-1 could prevent DC maturation and induce immune tolerance of transplanted organs.
Methods: DCs were transduced with a recombinant lentiviral vector to inhibit Dectin-1 and then were injected into a murine recipient before islet transplantation. C57BL/6 mice (H-2b) were treated with lentiviral vector-Dectin-1-RNAi-DC (DC-Dectin-1-RNAi group), lentiviral vector-GFP DCs (DC-GFP group), and PBS (control group). Pancreatic islet transplantation was performed and graft survival was recorded. The proportions of regulatory T cells, Th1 cells, and Th17 cells in the spleen and draining lymph nodes, and serum levels of interleukin (IL)-10, IL-17, and interferon (INF)-γ were measured.
Results: The inhibition of Dectin-1 resulted in low expression of MHC-II and costimulatory molecules in DCs. Murine recipients treated with DC-Dectin-1-RNAi had longer islet allograft survival time, a reduction in the levels of Th1 and Th17 cells and secreted cytokines, and an increase of Treg cells.
Conclusion: The inhibition of Dectin-1 by recombinant lentiviral vector Dectin-1-RNAi inhibits the maturation and activation of DCs, affects the differentiation of T cell subsets, and prolongs allograft survival.

Keywords: dendritic cell, Dectin-1, immune tolerance, islet transplant, lentiviral vector


中文翻译：

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抑制树突状细胞上的 Dectin-1 可防止成熟并延长小鼠胰岛同种异体移植物的存活时间

简介：树突状细胞 (DC) 启动免疫反应或诱导免疫耐受的能力取决于其成熟状态。树突状细胞相关的 C 型凝集素 1 (Dectin-1) 在 DC 的分化、激活和成熟中起关键作用。因此，我们假设抑制 Dectin-1 可以阻止 DC 成熟并诱导移植器官的免疫耐受。
方法：DCs 用重组慢病毒载体转导以抑制 Dectin-1，然后在胰岛移植前注射到小鼠受体中。用慢病毒载体-Dectin-1-RNAi-DC（DC-Dectin-1-RNAi组）、慢病毒载体-GFP DCs（DC-GFP组）和PBS（对照组）处理C57BL/6小鼠（H-2b） ）。进行胰岛移植并记录移植物存活率。测定脾脏和引流淋巴结中调节性T细胞、Th1细胞和Th17细胞的比例，以及白细胞介素（IL）-10、IL-17和干扰素（INF）-γ的血清水平。
结果：Dectin-1 的抑制导致 DCs 中 MHC-II 和共刺激分子的低表达。用 DC-Dectin-1-RNAi 治疗的小鼠受体具有更长的胰岛同种异体移植物存活时间，Th1 和 Th17 细胞和分泌的细胞因子水平降低，Treg 细胞增加。
结论：重组慢病毒载体Dectin-1-RNAi对Dectin-1的抑制作用可抑制DCs的成熟和活化，影响T细胞亚群的分化，延长同种异体移植物的存活时间。

关键词：树突状细胞，Dectin-1，免疫耐受，胰岛移植，慢病毒载体