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

项目总结 虽然外源DNA介导的免疫应答有助于宿主防御，但过量的宿主细胞质 由于干扰素的过度生产，DNA可能会导致自身免疫性疾病。紫杉素α(TXLNA)已被 隐含在胞浆DNA引起的自身免疫性疾病中。然而，TXLNA在DNA介导的先天性中的作用 豁免权是未知的。因此，迫切需要阐明TXLNA如何调节DNA诱导的机制 先天免疫信号。这一应用提出了一种假设，即TXLNA是一种新的信号分子 DNA介导的、干扰素依赖的先天免疫。目标1将建立TXLNA作为TBK1的调节器 DNA介导的体内和体外天然免疫。TXLNA缺乏将建立要求和 Tbk1介导的干扰素激活对DNA反应的特异性。Aim 2将研究这些机制 通过TXLNA调节DNA介导的先天信号通路中的TBK1活性。我们将研究几个 TXLNA介导的TBK1激活和募集到刺痛信号体的假说。机械论 这项建议所衍生的概念，将促进我们目前对 DNA介导的先天免疫。该项目还将为研究生和本科生提供 为进入生物医学科学事业做准备的重大独立研究的机会。

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.