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中文摘要
翻译
黄病毒、视黄酸诱导基因1蛋白(RLG-1)的主要感受器与黑色素瘤分化 抗原5(MDA5;也称为1F1H1)和LGP2(也称为DHX58)在近 体内的所有细胞类型,并在病毒感染期间和对I型病毒的反应中诱导水平升高 作为下游的接头蛋白,线粒体抗病毒信号(MAV)也广泛表达。 这使得很难准确地定义在哪些细胞中以及何时这些传感器通路对先天的 免疫学或免疫病理学。尽管使用条件性敲入(K1)小鼠的进展,用牙线 小鼠的先天免疫信号成分要么还没有被基因鉴定,要么还没有被广泛使用。 这一核心将通过开发和提供K1小鼠来帮助调查人员,在K1小鼠中 传感器(RIG-1、MDA5、LPG2)、信号元件(MAV、IFNR、IL28RA、1L-1R)或细胞因子(BAFF、IL-IBeta) 在树突状细胞(DC)或巨噬细胞等先天免疫细胞中被选择性地敲除,或者在 B细胞、CD4T细胞或神经元。Core还将开发一组新颖的报告老鼠,以便先天 病毒感染后很容易检测到IFNB、1L-1B和BAFF等免疫细胞因子。这个核心很可能是 通过提供这些新型小鼠,显著影响天然免疫和病毒免疫学领域 资源。
英文摘要
The major sensors of flaviviruses, retinoic acid-inducible gene 1 protein (RlG-1), melanoma differentiation antigen 5 (MDA5; also known as 1F1H1) and LGP2 (also known as DHX58), are expressed basally in nearly all cell types in the body and are induced to increased levels during viral infection and in response to type I IFNs The downstream adaptor protein, mitochondrial antiviral signaling (MAVS) is also broadly expressed. This makes it difficult to define exactly in which cells and when these sensor pathways are critical for innate immunity or immunopathology. In spite of the advances of using conditionally knocked in (Kl) mice, floxed mice for innate immune signaling components either have not been gene rated or have not been used widely. This Core will help investigators by developing and providing investigators with Kl mice in which key viral sensors (RIG-1, MDA5, LPG2), signaling elements (MAVS, IFNR, IL28RA, 1L-1R) or cytokines (BAFF, IL-IBeta) have been selectively knocked out in innate immune cells such as dendritic cells (DC) or macrophages or in B cells, CD4 T cells or neurons. The Core will also develop a set of novel reporter mice so that innate immune cytokines like IFNB, 1L-1B and BAFF can be readily detected after viral infections. This Core is likely to significantly impact the field of innate immunity and viral immunology by providing these novel mouse resources.
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Development of Novel CD180-Based Cancer Immunotherapeutics
  • 批准号:
    10381384
  • 项目类别:
  • 资助金额:
    $39.8万
  • 财政年份:
    2022
  • 负责人:
    Edward A Clark
  • 依托单位:
Establishing and characterizing BAFF RFP reporter and BAFF knockin mice
  • 批准号:
    8468991
  • 项目类别:
  • 资助金额:
    $8.9万
  • 财政年份:
    2012
  • 负责人:
    Edward A Clark
  • 依托单位:
Establishing and characterizing BAFF RFP reporter and BAFF knockin mice
  • 批准号:
    8353277
  • 项目类别:
  • 资助金额:
    $8.9万
  • 财政年份:
    2012
  • 负责人:
    Edward A Clark
  • 依托单位:
Regulation of B cell responses to West Nile Virus Infections
  • 批准号:
    7746284
  • 项目类别:
  • 资助金额:
    $31.7万
  • 财政年份:
    2009
  • 负责人:
    Edward A Clark
  • 依托单位:
海外基金