全基因扫描技术证实白介素-1受体相关激酶1（IRAK1）是SLE发病的易感基因，而IRAK1与多种免疫炎症性疾病密切相关，并推测IRAK1可通过介导IL-1R/TLR信号途径诱导Th17细胞的功能异常。本课题选择IRAK1为切入点，以SLE患者为研究对象，在前期已明确IRAK1基因外显子单倍型在SLE存在显著差异工作基础上，分析SLE患者不同单倍型的Th17相关转录因子表达和功能的差异及其与临床关联性。构建IRAK1基因外显子区不同突变位点载体，借荧光素酶报告基因、染色体免疫共沉淀等方法，观察对Th17下游相关转录因子功能的影响及可能机制。在此基础上，选择狼疮鼠动物模型，观察给予不同表达的基因载体对狼疮炎症活动的影响。本研究将易感基因与SLE免疫性炎症形成有机结合，探讨炎症信号通路调控SLE免疫异常及其与炎症形成的关系，为开展选择性关闭炎症信号通路的生物治疗提供依据。

The gene of interleukin-1-receptor-associated kinase 1(IRAK1),known as an gene for close relationship with many kinds of immune inflammatory diseases, has been found to be associated with the susceptibility of systemic lupus erythematosus(SLE) patients with genome-wide analyses from various global areas. It has been postulated that IRAK1 may regulate the dysfunctions of Th17 cells mediated by IL-1R/TLR signal pathways. In our previous work,we found that there is much difference of IRAK1 haplotypes between SLE patients and nomal subjects. In present project, the expression levels and functions of associated ranscription factors on periphery blood Th17 cells from patients with SLE will be detected by real-time PCR and immuno-blotting respectively based on different haplotypes and will be analysed to be associated with clinical phenotypes of SLE patients based on different IRAK1 haplotypes .From these bases on,co-expression vehicles containing different mutants of IRAK1 will be constructed and transferred into Th17 cells. Then, Effects on both the expression levels and functions of correlated transcription factor of Th17 cells will be observed in transferred cells.The anti-inflammatory effects with different mutants will be explored in C57/6-lpr mice. The aims of this project are to make a close connection between predisposing genes and immune-mediated inflammmation of SLE,and to explore the relationship between inflammation formation and immune disturbance of SLE mediated by inflammatory signaling pathways and to provide some novel evidences to establish biologic therapies on slectively turning off inflammatory signal to treat SLE.