宿主遗传背景对细胞因子应答的调控是结核易感性的重要机制。Th17及其效应分子IL-17A在结核保护性免疫中起着重要作用，但IL17A基因多态性与结核病易感性的关系尚无报道。我们前期发现IL17A基因及调控Th17分化的IL1B/TGFB/IL6基因的多个SNP与结核病相关。本项目拟采用高通量芯片技术对IL1B/TGFB/IL6/IL17A基因SNP进行大样本病例对照研究，明确上述基因SNP及其交互作用与结核病发生的相关性；研究易感基因SNP对IL1B/TGFB/IL6/IL17A基因转录和表达的影响，明确易感基因SNP对IL-17A应答的调控作用；探讨易感基因SNP对基因的核蛋白结合能力、启动子活性、以及IL-17A信号通路蛋白STAT3活化的影响，阐明其对IL-17A应答的调控机制。项目完成，不仅为结核病免疫防治提供新的思路，同时为结核高危人群的早期筛查及其预防干预决策提供科学依据。

Tuberculosis is a complex diseases caused by Mycobacterium tuberculosis infection. Host genetic plays an important role in controling susceptibity or resistance to tuberculosis.In particular, polymorphisms in cytokine genes regulate cytokines response against mycobacterium tuberculosis infection, which, in turn,contribute to different susceptibility to tuberculosis. Although it has been recognized that Th17 cell and its effector cytokine, IL-17A, play an protective role in tuberculosis,the association between genetic polymphism in IL17A gene and tuberculosis has not been established. Our previous findings showed that not only single-nucleotide polymorphism (SNP) in Il17A, but also SNPs in IL6/TGFB gene , which encode cytokines for Th17 differentiation,are associated with tuberculosis. In this study, we are going to investigate the association between IL1B/TGFB/IL6/IL17A SNP and tuberculosis in large disease-control samples. The risk of individal SNP and cumulative risk of SNPs will be calculated. In addition, the function of those SNPs associated with TB on regulation of cytokine response in tuberculosis will be defined. Finally, we will investigate the mechanism how those SNPs modulate IL-17 response and its clinical significance in pathogenesis of tuberculosis. The results of this study will provide new insight to the pathogenesis of tuberculosis and highlight potential target for the immunotherapy of tuberculosis. At the same time, SNPs associated with susceptibility to tuberculosis could be used for assessing the risk of tuberculosis in high risk population.