Lnc-PINK regulation of innate immunity in lung epithelial cells

项目总结 流感病毒感染呼吸道，可能导致急性呼吸窘迫综合征和 肺炎与高死亡率相关。该项目的长期目标是了解 肺上皮细胞如何响应和限制呼吸道病毒感染的分子机制。先天的 免疫是呼吸道病原体入侵的第一反应者，是人类免疫的第一道防线。 阿龙。从而通过靶向肺上皮宿主来增强宿主对呼吸道病毒的防御反应 因子是一种无论病毒发生任何变化都限制呼吸道病毒感染的策略。长非编码 RNAs(LncRNAs)是一种与mRNAs类似的转录产物，其大小为200个核苷酸，但不编码蛋白质 并参与多种细胞过程，包括先天免疫。通过RNA测序分析 和分子克隆，我们已经在肺上皮细胞中鉴定出一种新的lncRNA转录本，lnc-PINK1-2：5 减少流感病毒感染并上调硫氧还蛋白相互作用蛋白(TXNIP)的表达 这会激活NLRP3炎症。基于这一初步数据，我们假设LNC-PINK1-2：5 上调TXNIP基因激活NLRP3炎性小体抑制呼吸道病毒感染 在肺上皮细胞中表达。目的确定lnc-PINK1-2：5在流感病毒中的功能作用。 人肺上皮细胞感染。AIM II将阐明lnc-PINK1-2：5-的分子机制 流感病毒在人肺上皮细胞中的介导限制。

PROJECT SUMMARY The influenza virus infects the respiratory tract and may result in acute respiratory distress syndrome and pneumonia associated with a high mortality rate. The long-term goal of this project is to understand the molecular mechanisms how the lung epithelial cells responds to and restricts respiratory virus infection. Innate immunity is the first responder to respiratory pathogen invasion and provides the first line of defense in the lung. Thus enhancing the host defense response against respiratory virus by targeting lung epithelial host factors is a strategy to restrict respiratory virus infection regardless of any viral changes. Long non-coding RNAs (lncRNAs) are mRNA-like transcripts with a size of > 200 nucleotides, but that do not encode proteins and are involved in diverse cellular processes including innate immunity. Through RNA sequencing analysis and molecular cloning, we have identified a novel lncRNA transcript, lnc-PINK1-2:5 in lung epithelial cells that reduces influenza virus infection and up-regulates the expression of thioredoxin interacting protein (TXNIP) that activates NLRP3 inflammasomses. Based on this preliminary data, we hypothesized that lnc-PINK1-2:5 restricts respiratory virus infection by activating NLRP3 inflammasomes via upregulating TXNIP gene expression in lung epithelial cells. Aim I will establish the functional roles of lnc-PINK1-2:5 in influenza virus infection of human lung epithelial cells. Aim II will delineate the molecular mechanisms of lnc-PINK1-2:5- mediated restriction of influenza virus in human lung epithelial cells.