组织定居性记忆T细胞（Resident-Memory T cells, TRM）在抗感染中发挥至关重要的作用，但肺组织TRM的抗感染作用与作用机制依然不清。本项目拟在已经建立的低致病性流感病毒H9N2感染小鼠建立TRM基础上，利用内源基因高度同源的高致病性H7N9感染小鼠，建立攻击-保护模型观察TRM的抗流感作用；同时，对比观察TRM存在与缺失、关键基因敲除与未敲除小鼠在H7N9攻击后的生存情况，以确认TRM保护作用及介导保护的关键基因；利用RNA-Seq获取转录组数据，对比分析TRM再次应答前与应答后自身及肺组织的免疫应答，系统解析TRM介导的免疫应答及其对肺组织免疫微环境的作用；经原位杂交与免疫荧光技术，验证RNA-Seq分析数据。本项目将较系统解析肺组织TRM抗流感的作用机制，对研究肺组织TRM抗其他病原体感染有借鉴价值，为研制保护效果更佳的抗呼吸道病原体疫苗及临床免疫干预奠定基础。

Resident-memory T cells (TRM) play a critical role in protection from pathogen infection, however, it remains to be defined for the role of lung TRM in protective immunity against Influenza. We previously established an H9N2 (low pathogenic virus) infection model to characterize lung TRM. On top of this model, we will employ highly pathogenic H7N9 Influenza to attack previously H9N2-infected mice to test the protective effect of lung TRM (This model will minimized the inference from antibody-mediated protection), compare the survival of mice in the presence versus absence of TRM, key gene knockout versus intact to corroborate TRM-mediated protection and determine the key protective gene; Meanwhile, comparative analyses will be performed on RNA-seq data from TRM before versus after secondary responses (TRM itself and lung tissues) to decipher TRM-mediated protection mechanism; These data will be further confirmed by in site RNA hybridization and immune fluorescence staining. Overall these project aims to unfold the lung TRM working mechanism during Influenza infection, the data extracting from this project will highly enlighten other researches on lung TRM during other microbe infections and on the development of vaccine against respiratory pathogens and of immune intervention strategies.