Regulating Interferon signalling in innate immunity

我们的先天免疫系统进化成了抵御感染的前线防御系统。然而，失控的反应可能导致严重的疾病，如感染性休克，慢性炎症，如肝炎，自身免疫性疾病，如系统性红斑狼疮。在这些情况下，免疫反应受到重要荷尔蒙的调节，如身体产生的干扰素。该项目旨在了解在不限制干扰素的积极或有益影响的情况下，防止干扰素的危险副作用的负面或抑制机制。我们将研究一种名为细胞因子信号转导抑制因子1(SOCS1)的分子的作用，我们最近发现这种分子可以调节小鼠体内干扰素的作用。最初，我们的研究将确定SOCS1与细胞内的哪些分子结合，以及对细胞激活途径的影响。下一步将专门阻断小鼠体内的这种相互作用，并确定对病毒感染和炎症性疾病模型的影响。这些研究的结果将是更好地了解人体如何通过免疫反应与疾病作斗争，以及开发治疗药物的潜在新方法。

Our innate immune system evolved as the front line defence against infection. However an uncontrolled response can lead to serious diseases such as septic shock, chronic inflammation as in hepatitis, autoimmune diseases such as systemic lupus erythematosus. The immune respnse is regulated by important hormones such as interferon produced by the body in these situations. This project aims to understand the negative or inhibitory mechanisms that prevent dangerous side effects of interferons without restricting their postive or beneficial effects. We will examine the actions of a molecule called the Suppressor of cytokin Signaling 1 (socs1) which we have recently discovered to modulate the actions of interferon in the mouse. Initially our studies will determine which molecules SOCS1 binds to inside a cell and the consequences for cell activation pathways. The next step will be to specifically block this interaction in the mouse and determine the effects on models of viral infection and inflammatory disease. The outcome of these studies will be a better understanding of how the body fights disease via the immune response and potential new approaches to develop therapeutic drugs.