Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation.
Multiple Immunosuppressive Effects of CpG-c41 on Intracellular TLR-Mediated Inflammation.
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CpG-c41 对细胞内 TLR 介导的炎症的多重免疫抑制作用
DOI：
10.1155/2017/6541729
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发表时间：
2017
影响因子：
4.6
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Liu W;Yang X;Wang N;Fan S;Zhu Y;Zheng X;Li Y
越来越多的文献表明，大多数慢性自身免疫性疾病与Toll样受体（TLR）3、TLR 7/8或TLR 9介导的不适当炎症有关。因此，研究阻断TLR活化以治疗这些疾病已成为一个热门话题。在这里，我们报告的免疫调节特性的非刺激性的含CpG的寡脱氧核苷酸（CpG-ODN），CpG-C41，这以前只被称为TLR 9拮抗剂。在这项研究中，我们发现体外和体内CpG-c41都降低了各种促炎因子的水平，这些促炎因子是由细胞内TLR的单一激活或共激活诱导的，但不是膜结合TLR，无论TLR依赖于什么下游信号通路。CpG-c41减弱了咪喹莫特诱导的银屑病中的过度炎症-通过抑制免疫细胞浸润和炎性因子的释放来抑制皮肤炎症的小鼠模型。我们还发现CpG-c41对其他细胞内TLR的免疫抑制作用是由TLR 9非依赖性机制介导的。这些结果表明，CpG-c41作为信号级联的上游，可能在配体内化和转移的过程中。总之，这些结果表明，CpG-c41破坏细胞内TLR激活的各个方面，并提供了更深入的了解先天免疫的调节。
A growing body of literature suggests that most chronic autoimmune diseases are associated with inappropriate inflammation mediated by Toll-like receptor (TLR) 3, TLR7/8, or TLR9. Therefore, research into blocking TLR activation to treat these disorders has become a hot topic. Here, we report the immunomodulatory properties of a nonstimulatory CpG-containing oligodeoxynucleotide (CpG-ODN), CpG-c41, which had previously only been known as a TLR9 antagonist. In this study, we found that both in vitro and in vivo CpG-c41 decreased levels of various proinflammatory factors that were induced by single activation or coactivation of intracellular TLRs, but not membrane-bound TLRs, no matter what downstream signal pathways the TLRs depend on. Moreover, CpG-c41 attenuated excessive inflammation in the imiquimod-induced psoriasis-like mouse model of skin inflammation by suppressing immune cell infiltration and release of inflammatory factors. We also found evidence that the immunosuppressive effects of CpG-c41 on other intracellular TLRs are mediated by a TLR9-independent mechanism. These results suggest that CpG-c41 acts as an upstream of signaling cascades, perhaps on the processes of ligand internalization and transfer. Taken together, these results suggest that CpG-c41 disrupts various aspects of intracellular TLR activation and provides a deeper insight into the regulation of innate immunity.