探讨不同TLR信号级联间相互干扰的抑炎作用机制，对寻找用于控制和治疗自身免疫性疾病的新策略具有十分重要的意义。本课题组前期发现一种无免疫刺激性CpG-c41分子，它与TLR9结合并发生"无刺激内化"状态后，能交叉干扰LPS诱导TLR4信号级联的部分通路，抑制IL-6和IFN-β释放,而不影响TNF-a释放。虽干扰位置已锁定在局部范围，但具体干扰环节、作用方式等机制尚不清楚。本课题拟采用细胞免疫、激光共聚焦定位、定量PCR、蛋白磷酸化检测等技术，针对CpG-c41诱导TLR9无刺激内化干扰LPS/TLR4信号级联模型，对比观察TLR9与TLR4受体介导内化的效能，在内体循环过程中CpG-c41与LPS的转运状况，以及信号关键信号分子的活动状况。从而阐明TLR9无刺激内化对TLR4信号级联的负调控方式与作用环节，全面揭示其窜扰机制，为未来抗炎抗过敏及自身免疫性疾病治疗提供新的理论依据和策略。

Exploring anti-inflammation mechanism caused by the cross interference in different TLR signal pathways is very important for new strategy to prevent and treat the autoimmune diseases. In previous study, we found a novel non-stimulatory CpG-c41 molecule, which is able to lead to non-stimulatory endocytosis after binding with TLR9. Under this situation, a potential crosstalk disturbed the part of the signal pathways in the LPS induced TLR4 cascade, suppressing the release of IL-6 and IFN-β，but not that of the TNF-a. Although the target region was at the range from TLR4 internalization to the binding of TRAM/TRIF, it is still obscure about the detailed mechanism of the non-stimulatory endocytosis of TLR9 cross-interfering with the TLR4 signal cascade. In this study, using the cellular immunofluorescence staining and confocal laser scanning technique, quantitative real-time PCR and phosphorylation examination by Western Blot,etc, based on the model of CpG-c41 induced TLR9 non-stimulatory endocytosis disturbing the LPS induced TLR4 signal cascade, we observe the different performances between TLR4 and TLR9 mediated endocytosis, the trafficking of LPS and CpG-c41 in the dynamic endosomal cycling, the activities of key signal molecules, in order to illustrate the negative regulatory process and the action target during the crosstalk of different TLR mediated endocytosis, and reveal the detailed mechanism of cross interference. This study would provide logical proofs and new stategy to the future therapies for inflammatory, allergic and other autoimmune diseases.