系统性红斑狼疮易感基因NCF1及其SNP rs201802880在浆细胞样树突状细胞活化中的功能和机制研究

系统性红斑狼疮(systemic lupus erythematosus , SLE) 是一种复杂、异质性的自身免疫病，和遗传密切相关。浆细胞样树突状细胞（Plasmacytoid dendritic cells，pDCs）作为I型干扰素产生的主要细胞亚群，被证实在自身免疫性疾病中起关键作用。我们前期的研究发现了NCF1基因编码区一个错义突变的SNP位点R90H（rs201802880）与SLE等自身免疫病显著相关，但NCF1基因及其SNP在SLE疾病中的功能尚不清楚。因此，本项目将对NCF1在pDC中的功能和作用机制进行研究。在此基础上，利用pDC SNP细胞系和SNP小鼠，通过质谱、co-IP等方法，研究该突变对NCF1蛋白功能的影响。进一步，利用诱导狼疮小鼠模型评价不同基因型SNP小鼠的发病情况，从而阐明该突变位点在SLE发病中的作用，为SLE等自身免疫病的诊断和治疗提供基础。

Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease closely related to heredity. Plasmacytoid dendritic cell (pDC), a major type I interferon producing cell subset, is considered as a critical pathogenic cell in autoimmune diseases. Our previous study identified a SNP site rs201802880 in the coding region of NCF1, which has a strong correlation with SLE. However, the function of NCF1 and its SNP in SLE have not been reproted before. In this work, we will study the function of NCF1 in pDC activation. Furthermore, the effect of SNP mutation on NCF1 will be studied by using the SNP pDC cell line and SNP mice. Meanwhile, the involvement of SNP in lupus will be evaluated by using induced lupus mice models. Therefore, our work will clarify the role of NCF1 and its SNP in SLE, and suggest new target and treatment for autoimmune diseases.