Negative regulation of inflammation during Klebsiella pneumoniae infection

项目摘要 肺炎克雷伯氏菌（KP）感染激活IL-17信号通路，这对抑制KP至关重要 传播和促进病原体根除。在此过程中，IL-17受RNA负调控， 结合蛋白（RBP），以减少宿主的附带组织损伤。这些限制性商业惯例之一是 Regnase-1（Reg 1），通过编码区或3 'UTR降解IL-17诱导的转录物。在这 建议，我们将调查的作用，Reg 1在气道上皮在KP肺炎。我们假设 Reg 1缺陷增强了气道上皮中促炎转录物的作用， 对KP的豁免权。为此，我们将描述气道上皮中Reg 1条件性敲除的特征， 以及研究Reg 1在表观遗传和转录后水平的调控。

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.