全球多个地区报道用全基因扫描技术从SLE患者中都筛选到相关的易感基因TNFAIP3，而TNFAIP3又是TNFα介导的NF-κB信号途径异常活化的重要负性调控分子。本课题选择TNFAIP3为切入点，以SLE患者为研究对象，采用SNP分析、定量PCR等技术，观察患者外周血T细胞亚群中TNFAIP3mRNA和蛋白表达水平及基因多态性，分析其与临床关联性。在此基础上，体外构建不同基因型别的共表达载体，作用于Jurkat细胞，观察TNF和脂多糖作用后细胞炎症信号分子的变化，同时观察不同基因型别表达的蛋白对狼疮鼠体内炎症反应的影响，以明确TNFAIP3调控SLE自身免疫炎症形成的分子缺陷及其信号变化特征。本研究可望为解释SLE患者病情多样化和重症化提供全新的依据，为建立选择性关闭SLE炎症信号的个体化疗法提供新的分子靶位。

The gene of tumor necrosis factor alpha-induced protein3(TNFAIF3),known as one of important endogenous negative regulators of TNFα mediated NF-κB inflammatory singnaling, has been found to be associated with the susceptibility of systemic lupus erythematosus(SLE) patients with genome-wide analyses from various global areas. However, the molecule evidences of deficient functions of TNFAIF3 to regulate the inflammation of SLE are still unclear.In present project, the expression levels of TNFAIF3 mRNA and protein on periphery blood T subgroup cells from patients with SLE will be detected by real-time PCR and immuno-blotting respectively and the mutations of TNFAIF3 gene will be analysed to be associated with clinical phenotypes of SLE patients by single nucleotide polymorphisms(SNPs).From these bases on,co-expression vehicles containing different genotypes will be constructed and transferred into Jurkat cells. Then, the diversify pattens of inflammatory signaling activation in transferred Jurkat cells will be observed by Western blotting following the stimulations of tumor necrosis factor alpha or lipopolysaccharide（LPS）.The anti-inflammatory effects with different mutants will be explored in C57/6-lpr mice. The aims of this project are to explore the molecule deficient basis and mechanism of function failure of TNFAIF3 to negatively regulate the activation of NF-κB inflammatory signaling pathways which induce auto-inflammatory processes of SLE and to provide some novel evidences about both the elucidation of illness diversification and the findings of new molecular targets to treat SLE.