结核是全球最致命的慢性传染病，尚无有效疗法。MAIT细胞在早期抗结核免疫反应中发挥关键作用，靶向控制MAIT细胞可能是改善疫苗功效和治疗结核病的有效方法。但目前对于结核特异性MAIT细胞的信号调控机制仍知之甚少。课题组率先开展mTORC1调控PLZF在MAIT细胞抗结核免疫中的效应与机制研究，前期利用MR1四聚体结合流式细胞术对133名活动性结核患者外周血MAIT细胞进行初步分析发现，MAIT细胞在结核感染免疫中发挥重要作用。在此基础上，拟：①利用MR1四聚体进一步明确MAIT细胞的抗结核作用；②确定mTORC1对MAIT细胞抗结核效应的调控作用；③阐明mTORC1在PI3K-AKT和DAG-RasGRP1-Ras-ERK1/2信号通路诱导下，通过调控PLZF调节MAIT细胞抗结核效应的机制。项目为开发新型抗结核免疫疗法提供思路和潜在治疗靶标。

Tuberculosis (TB) is the world’s deadliest chronic contagion. Currently there is no effective treatment for this disease. It has been noted that the mucosal associated invariant T (MAIT) cells play an important role in the early anti-TB immune response. Targeted control of MAIT cells may be an effective way to improve vaccine efficacy and treat TB. However, little is known about the signal regulation mechanism of the TB specific MAIT cells. The research group is the first to carry out the study on the regulatory effects and mechanisms of PLZF by mTOC1 in MAIT cells-mediated immunity to Mycobacterium tuberculosis (MTB). After using MR1 tetramer to analyze MAIT cells in the peripheral blood of 133 active TB patients, our results showed that MAIT cells play an important role in the anti-TB immune response. On this basis, it is proposed to: (1) The anti-TB effect of MAIT cells is further determined by using MR1 tetramer; (2) Determine the regulatory effects of mTORC1 on the anti-TB activity of MAIT cells; (3) Clarify the mechanisms that the anti-TB activity of MAIT cells is controlled by mTORC1 which is activated by the PI3K-AKT and DAG-RasGRP1-Ras-ERK1/2 signaling pathway through regulating PLZF. The project provides ideas and potential therapeutic targets for the development of new TB immunotherapy.