DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals.
DNA and protein co-administration induces tolerogenic dendritic cells through DC-SIGN mediated negative signals.
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DNA 和蛋白质共同给药通过 DC-SIGN 介导的负信号诱导耐受性树突状细胞
DOI：
10.4161/hv.25011
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发表时间：
2013-10
影响因子：
4.8
通讯作者：
Wang B
中科院分区：
文献类型：
--
作者：
Li J;Geng S;Liu X;Liu H;Jin H;Liu CG;Wang B
我们先前证明，DNA和蛋白质的共同管理诱导未成熟的树突状细胞（iDCs）分化为CD 11 c + CD 40 lowIL-10+调节性DCs（DCDC）通过小窝蛋白-1（Cav-1）介导的信号通路。在这里，我们证明了IL-10的产生和CD 40的低表达在随后的DC诱导的调节性T细胞（TCLs）中起着关键作用。我们观察到，DNA和蛋白质与DC-SIGN共定位在处理的DC中的小窝和早期溶酶体中，如通过与Cav-1和EEA-1隔室标记物的共定位所指示的。DNA和蛋白质也与LAMP-2共定位。基因表达的基因阵列分析显示，与对照组相比，DC与DNA +蛋白质共处理显著改变了一千多个基因。值得注意的是，DC-SIGN表达水平在pOVA + OVA共处理的DC中显著上调。DC-SIGN介导的信号通路的下游分子Rho和RhoGNEF的表达水平也显著上调。此外，传统的DNA受体TLR 9的水平显著下调。这些结果表明DC-SIGN作为DNA和蛋白质的潜在受体可能触发负性信号通路，从而促进DCreg与Cav-1介导的负性信号通路的结合。
We previously demonstrated that DNA and protein co-administration induced differentiation of immature dendritic cells (iDCs) into CD11c+CD40lowIL-10+ regulatory DCs (DCregs) via the caveolin-1 (Cav-1) -mediated signal pathway. Here, we demonstrate that production of IL-10 and the low expression of CD40 play a critical role in the subsequent induction of regulatory T cells (Tregs) by the DCregs. We observed that DNA and protein were co-localized with DC-SIGN in caveolae and early lysosomes in the treated DCs, as indicated by co-localization with Cav-1 and EEA-1 compartment markers. DNA and protein also co-localized with LAMP-2. Gene-array analysis of gene expression showed that more than a thousand genes were significantly changed by the DC co-treatment with DNA + protein compared with controls. Notably, the level of DC-SIGN expression was dramatically upregulated in pOVA + OVA co-treated DCs. The expression levels of Rho and Rho GNEF, the down-stream molecules of DC-SIGN mediated signal pathway, were also greatly upregulated. Further, the level of TLR9, the traditional DNA receptor, was significantly downregulated. These results suggest that DC-SIGN as the potential receptor for DNA and protein might trigger the negative pathway to contribute the induction of DCreg combining with Cav-1 mediated negative signal pathway.
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DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Geijtenbeek TB;Gringhuis SI
通讯作者：
Gringhuis SI
影响因子：
8.6
作者：
Knisz, Judit;Banks, Alex;Brown, Jared M.
通讯作者：
Brown, Jared M.
影响因子：
64.8
作者：
PETERS, PJ;NEEFJES, JJ;GEUZE, HJ
通讯作者：
GEUZE, HJ
影响因子：
32.4
作者：
Cao, Xuefang;Cai, Sheng F.;Ley, Timothy J.
通讯作者：
Ley, Timothy J.
影响因子：
4.4
作者：
Ganesh, Balaji B.;Cheatem, Donald M.;Prabhakar, Bellur S.
通讯作者：
Prabhakar, Bellur S.