Taxilin Alpha Regulates DNA-Mediated and Interferon-Dependent Innate Immunity

Taxilin Alpha 调节 DNA 介导和干扰素依赖性先天免疫

• 批准号: 9303580
• 负责人: Shitao Li
• 金额: $ 43.18万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-06 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9303580
• 关键词: Animal Model; Autoimmune Diseases; Binding; DNA; DNA Virus Infections; DNA Viruses; Data; Development; Dimerization; Endoplasmic Reticulum; Environment; Genes; Health Sciences; Host Defense; Immune response; Immune signaling; Immunity; In Vitro; Interferon Activation; Interferon Type I; Interferons; Investigation; Knockout Mice; Link; Literature; Mediating; Natural Immunity; Oklahoma; Pathway interactions; Play; Polyubiquitin; Production; Proteomics; Recruitment Activity; Research; Role; Science; Signal Pathway; Signaling Molecule; Specificity; Systemic Lupus Erythematosus; TANK-binding kinase 1; Transgenic Mice; Treatment Efficacy; Universities; Virus Diseases; base; career preparation; dimer; graduate student; improved; in vivo; novel therapeutics; prevent; protein complex; response; undergraduate student

Project summary While exogenous DNA-mediated immune response contributes to host defense, excessive host cytoplasmic DNA can result in autoimmune diseases due to interferon overproduction. Taxilin alpha (TXLNA) has been implied in autoimmune disease caused by cytosolic DNA. However, the role of TXLNA in DNA-mediated innate immunity is unknown. Thus, it is pressing to elucidate the mechanisms of how TXLNA regulates DNA-induced innate immune signaling. This application proposes a hypothesis that TXLNA is a new signaling molecule in DNA-mediated, interferon-dependent innate immunity. Aim 1 will establish TXLNA as a TBK1 regulator in DNA-mediated innate immunity in vitro and in vivo. TXLNA deficiency will establish the requirement and specificity in TBK1-mediated interferon activation in response to DNA. Aim 2 will investigate the mechanisms by which TXLNA regulates TBK1 activity in DNA-mediated innate signaling pathway. We will examine several hypotheses of TXLNA-mediated TBK1 activation and recruitment to STING signalosome. The mechanistic concepts derived from this proposal will advance our current understanding of the regulatory mechanisms in DNA-mediated innate immunity. This project will also provide graduate and undergraduate students with opportunities for significant independent research in preparation for careers in biomedical science.

项目概要 虽然外源 DNA 介导的免疫反应有助于宿主防御，但过多的宿主细胞质 由于干扰素过量产生，DNA 可能导致自身免疫性疾病。塔西林α（TXLNA）已被 暗示由细胞质DNA引起的自身免疫性疾病。然而，TXLNA 在 DNA 介导的先天性中的作用 免疫力未知。因此，阐明TXLNA调控DNA诱导的机制迫在眉睫。 先天免疫信号。该申请提出了一个假设：TXLNA 是一种新的信号分子 DNA 介导的干扰素依赖性先天免疫。目标 1 将 TXLNA 建立为 TBK1 监管机构 DNA 介导的体外和体内先天免疫。 TXLNA 缺陷将建立要求并 TBK1 介导的干扰素激活对 DNA 的特异性。目标 2 将研究机制 TXLNA 通过 DNA 介导的先天信号通路调节 TBK1 活性。我们将检查几个 TXLNA 介导的 TBK1 激活和招募到 STING 信号体的假设。机械论 从该提案中得出的概念将增进我们目前对监管机制的理解 DNA 介导的先天免疫。该项目还将为研究生和本科生提供 为生物医学科学职业做准备的重要独立研究的机会。