Nucleic Acid Sensing by Innate Immune Receptors

先天免疫受体的核酸传感

• 批准号: MC_UU_00008/8
• 负责人: Jan Rehwinkel
• 金额: $ 366.46万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_UU_00008%2F8
• 关键词: Nucleic; Acid; Sensing; Innate; Immune

We are trying to work out how the immune system is activated in virus infection and inflammatory disease. Cells infected by virus respond by producing anti-viral factors, which block viral replication and help to control infection. We are interested in a cell molecule called RIG-I, which detects infection with viruses such as influenza A virus. RIG-I recognizes the presence of viral genomes made of RNA. However, normal cells also contain RNA as this is the ‘messenger’ molecule that allows the DNA genes of cells to be copied and translated into protein. How, then, can RIG-I distinguish between the RNA of the cell and the RNA of the virus? The answer lies in a structure called a ‘cap’ found at the starting point of cellular RNAs. Viral RNA genomes do not have this ‘cap’ and RIG-I specifically responds only to RNAs lacking this structure. This is why only cells infected by viruses produce anti-viral factors. By working out how RIG-I and other receptors detect infection with a variety of viruses we aim to understand how this type of immune response is controlled. In a second line of research, we are interested in inflammatory diseases such as Aicardi-Goutieres syndrome that result of the anti-viral pathways being triggered aberrantly in the absence of infection. We hope to determine how deregulation of these pathways can result in disease and find ways of controlling inappropriate inflammatory responses.

我们正试图弄清楚免疫系统是如何在病毒感染和炎症性疾病中被激活的。被病毒感染的细胞通过产生抗病毒因子来做出反应，这些抗病毒因子阻止病毒复制并有助于控制感染。我们感兴趣的是一种名为RIG-I的细胞分子，它可以检测甲型流感病毒等病毒的感染。RIG-I识别由RNA组成的病毒基因组的存在。然而，正常细胞也含有RNA，因为这是“信使”分子，允许细胞的DNA基因被复制并翻译成蛋白质。那么，RIG-I如何区分细胞RNA和病毒RNA呢？答案在于在细胞RNA的起始点发现的一种称为“帽”的结构。病毒RNA基因组没有这种“帽”，RIG-I只对缺乏这种结构的RNA有特异性反应。这就是为什么只有被病毒感染的细胞才能产生抗病毒因子。通过研究RIG-I和其他受体如何检测各种病毒的感染，我们的目标是了解这种免疫反应是如何控制的。在第二条研究线中，我们感兴趣的是炎症性疾病，如Aicardi-Goutieres综合征，这是在没有感染的情况下异常触发抗病毒途径的结果。我们希望确定这些通路的失调如何导致疾病，并找到控制不适当炎症反应的方法。

项目成果

Interferon induction held captive in tumor cells.

• DOI: 10.1016/j.molcel.2021.10.004
• 发表时间: 2021-10
• 期刊: Molecular cell
• 影响因子: 16
• 作者: A. Bridgeman;J. Rehwinkel

Type I interferon pathway assays in studies of rheumatic and musculoskeletal diseases: a systematic literature review informing EULAR points to consider.

• DOI: 10.1136/rmdopen-2022-002876
• 发表时间: 2023-03
• 期刊: RMD OPEN
• 影响因子: 6.2
• 作者: Burska, Agata;Rodriguez-Carrio, Javier;Biesen, Robert;Dik, Willem A.;Eloranta, Maija-Leena;Cavalli, Giulio;Visser, Marianne;Boumpas, Dimitrios T.;Bertsias, George;Wahren-Herlenius, Marie;Rehwinkel, Jan;Fremond, Marie-Louise;Crow, Mary K.;Ronnblom, Lars;Conaghan, P. G.;Versnel, Marjan;Vital, Ed
• 通讯作者: Vital, Ed

Hypoxia Regulates Endogenous Double-Stranded RNA Production via Reduced Mitochondrial DNA Transcription.

• DOI: 10.3389/fonc.2021.779739
• 发表时间: 2021
• 期刊: Frontiers in oncology
• 影响因子: 4.7
• 作者: Arnaiz E;Miar A;Dias Junior AG;Prasad N;Schulze U;Waithe D;Nathan JA;Rehwinkel J;Harris AL
• 通讯作者: Harris AL

cGAMP loading enhances the immunogenicity of VLP vaccines

• DOI: 10.1101/2020.01.03.893586
• 发表时间: 2020-01
• 期刊: bioRxiv
• 作者: Lise Chauveau;A. Bridgeman;T. Tan;R. Beveridge;Joe N. Frost;I. Pedroza-Pacheco;Thomas Partridge;P. Borrow;H. Drakesmith;A. Townsend;J. Rehwinkel

Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration.

• DOI: 10.1038/s41556-021-00707-9
• 发表时间: 2021-07
• 期刊: Nature cell biology
• 影响因子: 21.3
• 作者: Clapes T;Polyzou A;Prater P;Sagar;Morales-Hernández A;Ferrarini MG;Kehrer N;Lefkopoulos S;Bergo V;Hummel B;Obier N;Maticzka D;Bridgeman A;Herman JS;Ilik I;Klaeylé L;Rehwinkel J;McKinney-Freeman S;Backofen R;Akhtar A;Cabezas-Wallscheid N;Sawarkar R;Rebollo R;Grün D;Trompouki E
• 通讯作者: Trompouki E