申请者围绕阐明“结核感染中T细胞免疫调控机制”这一关键科学问题，取得主要成绩：⑴ 系统阐述了结核中IL-22的细胞膜结合特性、抗结核保护功能及Tim-3正调控IL-22的新机制（JI 2011，第1作者；PloS Pathogens 2012，独立通讯）；⑵深入研究了CD8+T细胞的抗结核功能及lncRNA调控CD8+T细胞效应功能的新机制（PNAS 2015，独立通讯）；⑶ 多层面阐述了T细胞过激炎症效应及IL-1β促进结核易感的新机制（BMC Immunology 2013，等），为深层次揭示结核发病机理并开发结核防治新技术提供了重要基础。发表SCI论文26篇，独立/并列通讯5篇，第一/并列第一6篇，总被他引294次，单篇他引最高83次。在已充分论证及预实验基础上，拟进一步发现可用于耐药结核防治的lncRNA表观遗传新靶点，并阐明其功能与机制，为解决结核“无药可治”危险局面提供新思路。

Elucidation of immune regulation mechanisms during tuberculosis (TB) infection is one of fundamental works to conquer the challenges in prevention and treatment of TB. Thus, I have been focusing on “elucidating the molecular mechanisms underlying immune suppression and over-activation mediated by T cells ” to uncover the novel immune regulation mechanisms during TB infection. I have also elucidated the membrane-bound property and anti-TB immune functions of IL-22(JI, 2011, 1st author). I have found that Tim-3 mediated a stronger but not inhibited T cell effector functions of IL-22 expression (PloS Pathogens, 2012, Corresponding author). I demonstrated the critical anti-TB role of CD8+T cells and demonstrated that lncRNA of CD8+T cells could serve as an important target to enhance CD8+T cell effector function to limit TB infection and reduce TB pathology(PNAS, 2015, Corresponding author ). I also elucidated the dual-edge role of T cell effector functions and inflammatory cytokines such as IL-1β. These works collectively help us to fully understand the immune regulation mechanisms leading to active TB disease and offer critical scientific bases for TB prevention and treatment. I have published 5 corresponding- authored papers, and 6 1st or co-1st authored papers, and a total of 26 papers. These papers had been collectively cited for 294 times by other scientists, and one of these 26 papers has the largest non-self citations of 83times. Bases on these previous results and our pilot studies, I will continuously discover novel lncRNA-based therapeutic targets for prevention and treatment of drug-resistant TB and elucidate the functions and mechanisms of this lncRNA-based strategy for prevention and treatment of drug-resistant TB. The on-going project will provide new insights into prevention and treatment of deadly TB disease.