Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival.
Inhibition of Dectin-1 on Dendritic Cells Prevents Maturation and Prolongs Murine Islet Allograft Survival.
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Dectin-1 对树突状细胞的抑制可防止树突状细胞成熟并延长小鼠胰岛同种异体移植物的存活
DOI：
10.2147/jir.s287453
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发表时间：
2021
影响因子：
4.5
通讯作者：
Ma Y
中科院分区：
文献类型：
--
作者：
Ren A;Li Z;Zhang X;Deng R;Ma Y
前言：树突状细胞(DC)启动免疫应答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、激活和成熟过程中起关键作用。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。方法用重组慢病毒载体转导抑制Dectin-1的DC，然后在胰岛移植前将其注射到受体小鼠体内。用慢病毒载体Dectin-1-RNAi-DC(DC-Dectin-1-RNAi组)、慢病毒载体-GFP DC(DC-GFP组)和PBS(对照组)治疗C57BL/6小鼠(H-2b)。行胰岛移植，记录移植物存活率。检测脾和引流淋巴结中调节性T细胞、Th1细胞和Th17细胞的比例，以及血清IL-10、IL-17和干扰素-γ水平。结果抑制Dectin-1后，DC表面MHC-II和共刺激分子表达降低。接受DC-Dectin-1-RNAi治疗的小鼠移植胰岛存活时间较长，Th1和Th17细胞水平及分泌的细胞因子水平降低，Treg细胞增加。结论慢病毒载体Dectin-1-RNAi抑制Dectin-1的表达可抑制DC的成熟和活化，影响T细胞亚群的分化，延长移植物存活时间。
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.