多发性硬化（MS）是中枢神经系统常见的脱髓鞘疾病，是青壮年致残的主要原因之一，目前尚缺乏有效的特异性免疫治疗手段。我们已经应用1,25-二羟维生素D3诱导了耐受性树突状细胞（DC），回输实验性自身免疫性脑脊髓炎（EAE）后，发现其对EAE有明显的治疗作用。在此基础上，本课题选择1,25-二羟维生素D3诱导耐受性DC过程中可能起关键作用的细胞内信号转导因子RelB和MyD88，研究其在EAE小鼠和MS患者DC中表达水平的变化；应用RelB和MyD88基因敲除鼠诱导EAE模型，研究RelB和MyD88在EAE发病中的作用；应用短发夹RNA（shRNA）沉默EAE小鼠和MS患者DC中RelB和MyD88的表达，诱导耐受性DC，然后将小鼠耐受性DC回输给已发病的EAE，研究其对EAE的治疗作用及机制（创新点），为临床应用耐受性DC特异性治疗MS提供新的方法和理论依据。

Multiple sclerosis is a common central nervous system demyelinating disease, which is one of the major disease causing young disability and lack of efficient method of specific immunotherapy. We induced tolerogenic dendritic cells (DCs) by 1,25-dihydroxyvitaminD3 in our previous study and found that these tolerogenic dendritic cells had obvious therapeutic effect on experimental autoimmune encephalomyelitis (EAE). Based on our previous studies, we choose RelB and MyD88, which may be the critical intracellular signal transduction molecules inhibited by 1,25-dihydroxyvitaminD3 during the induction of tolerogenic DCs and detect the alteration of these molecules in DCs of EAE and MS patients. To clarify the role of RelB and MyD88 in the pathogenesis of EAE, we will establish EAE animal model in RelB and MyD88 knockout mice. We will induce tolerogenic DCs from EAE and MS patients by silencing the expression of RelB and MyD88 in DCs with short hairpin RNA (shRNA). To investigate whether tolerogenic DCs induced by shRNA have the ability to ameliorate EAE, the tolerogenic DCs are intravenously injected into EAE mice. This study is supposed to provide a new method and the theoretical basis for the treatment of multiple sclerosis.