Rac1-p38β-IL6 通路介导的MSCs 免疫调节能力异常在强直性脊柱炎发病机制中的作用研究

强直性脊柱炎（AS）是一种患病率高、严重影响患者生活质量、发病机制不明的自身免疫炎症性疾病。我们发现AS 患者体内Th17/Treg 上调，而此比例上调已被证实在多种自身免疫炎症性疾病的发生及发展中起重要作用；同时我们在体外首次证实了AS患者骨髓间质干细胞（MSCs）免疫调节功能异常导致了Th17/Treg上调。AS患者MSCs通过何种途径导致了Th17/Treg上调尚不清楚？正常与AS患者MSCs表达谱基因芯片结果强烈提示Rac1-p38β-IL6 通路可能参与了此过程的调节，我们拟以此为切入点，在上述研究基础上，利用流式分析、特异性激动剂和抑制剂、RNAi等技术深入研究此通路在AS 患者MSCs免疫调节功能异常导致Th17/Treg上调中的作用，为阐明AS的发病机制提供理论依据，同时力图确定该通路中的关键节点分子及筛选新的干预靶点，为AS临床诊断及治疗提供新的思路。

Ankylosing Spondylitis(AS) is a severe chronic disease with high prevalence, characterized by autoimmune inflammation and pathological osteogenesis, of which the etiopathogenesis is still unclear. We have discovered the upregulation of Th17/Treg in AS patients, which plays significant role in the onset and development of many autoimmune-mediated inflammatory diseases. In addition, for the first time we have proved immunoregulatory dysfunction of AS patients' mesenchymal stem cells(MSCs) induces the upregulation of Th17/Treg. So the question is which pathway induces the change of Th17/Treg in AS patients? The gene expression profile chip results of normal and AS patients' MSCs strongly suggests the Rac1-p38 beta IL-6 pathway may be involved in this process. Based on our previous research, we intend to deeply study the role of this pathway in the regulation in Th17/Treg induced by MSCs' abnormal immunoregulatory ability using FACS(Fluorescence Activating Cell Sorter), specific agonist or antigonist, and RNAi technology, helping to elucidate the etiopathogenesis of AS , and in the same time try to determine the key molecules of this pathway and screen new intervention targets ,and finally provide a new method for AS clinical diagnosis and treatment.