调节性树突状细胞在脓毒症免疫紊乱过程中的作用及其机制

Previous study showed that treatment with purified natural regulatory dendritic cells (regulatory DC) isolated from BALB/c mouse spleen could effectively control the excessive inflammatory response in burn mice and markedly reduce early mortality by transfusion, which might provide a new method of immune conditioning mode - regulatory DC cell transfusion therapy. Recent studies suggest that signal transduction and activator of transcription -3 (STAT3) can induce the process of immune suppression, suggesting that regulatory DC may be mediated by STAT3 negatively regulate immune function. This project, based on preliminary studies, will illustrate the influence of STAT3 signaling pathway activation or inhibition on immune function of regulatory DC via flow cytometry, Western blot, EMSA, RNAi technology and quantitative PCR, respectively. Then, we will transfuse regulatory DC modified through STAT3 pathways activation or inhibition to septic mice for further investigating the potential role of STAT3 pathway in regulating DC function. The study will develop a new idea for treatment of sepsis by the enhanceed STAT3 signaling pathway in immune function of DC as an immune conditioning control treatment of sepsis - adoptive transfusion therapy.

申请人前期研究发现，通过回输纯化于BALB/c小鼠脾脏的天然调节性树突状细胞（regulatory DC, 调节性DC）可有效控制烧伤小鼠过度炎症反应并显著降低早期死亡率，从而为烧伤脓毒症寻求到了一种全新免疫调理治疗模式-调节性DC细胞回输治疗。新近研究提示信号转导及转录活化因子-3(STAT3)对诱导机体免疫抑制过程有影响，因此推测STAT3可能介导了调节性DC负向调控免疫功能的作用。本项目拟在前期研究基础上采用流式细胞技术、Western blot、EMSA、RNAi技术及定量PCR等方法，从STAT3信号通路角度分析STAT3活化或抑制对调节性DC免疫功能的影响；并将STAT3通路活化或抑制的调节性DC回输至脓毒症小鼠体内，进一步观察STAT3通路对调节性DC功能的影响。该研究为通过STAT3信号通路加强调节性DC免疫功能防治脓毒症的全新免疫调理治疗模式-过继回输治疗拓展新思路。