Negative regulation of inflammation during Klebsiella pneumoniae infection

项目摘要 肺炎克雷伯菌感染激活IL-17信号通路，这是抑制肺炎克雷伯菌的关键 传播和促进病原体根除。在这个过程中，IL-17受到RNA的负调控 结合蛋白(RBP)，以努力减少宿主的侧枝组织损伤。其中一个限制性商业惯例是 Regnase-1(REG1)，它通过编码区或3‘非编码区降解IL-17诱导的转录本。在这 建议，我们将研究REG1在肺炎期间呼吸道上皮细胞中的作用。我们假设 REG1缺乏增强了气道上皮中促炎症转录本的作用，这有利于 对KP的豁免权。为此，我们将描述呼吸道上皮细胞中的REG1条件性基因敲除 以及在表观遗传和转录后水平上研究REG1的调控。

Project Summary Infections with Klebsiella pneumoniae (KP) activate the IL-17 signaling pathway, which is crucial to constrain KP dissemination and facilitate pathogen eradication. During this process, IL-17 is negatively regulated by RNA binding proteins (RBP) in an effort to decrease collateral tissue damage in the host. One of these RBPs is Regnase-1 (Reg1) which degrades IL-17- induced transcripts either through the coding region or 3'UTR. In this proposal, we will investigate the role of Reg1 in the airway epithelium during KP pneumonia. We hypothesize that Reg1 deficiency enhances the effect of pro-inflammatory transcripts in the airway epithelium which favors immunity against KP. For that purpose, we will characterize a Reg1 conditional knockout in the airway epithelium upon KP pneumonia as well as investigate Reg1 regulation at the epigenetic and post-transcriptional level.