Characterizing a transcriptional control region within the Type I interferon gene cluster

项目摘要 I型干扰素（IFN-I）提供了抵抗病毒的第一道防线，并在协调 先天性和适应性免疫反应。传染性病毒的出现引发了一连串的事件 导致IFN-I基因的活化，进一步诱导大量抗病毒蛋白的表达。 这种抗病毒程序是必须选择性地诱导只有当适当的慢性 信号传导与严重的炎性表型和自身免疫有关。这些所谓 '干扰素病'是一种临床异质性疾病， 并谈到了在没有感染的情况下沉默IFN-1基因座的重要性。在此，我们建议 定义了一个被称为Kelch样家族成员9（KLHL 9）的保守基因是如何被发现的。 IFN-I基因簇，确保了在没有病毒感染的情况下该区域的转录抑制。这 拟议的研究将促进对IFN系统如何在免疫中心发挥作用的理解。 和炎症性疾病，也应该导致更好地了解分子原因， 至少是一种干扰素病

PROJECT SUMMARY Type I interferons (IFN-I) provide the first line of defense against viruses and play a pivotal role in coordinating the innate and adaptive immune responses. The presence of infectious viruses triggers a cascade of events leading to the activation of IFN-I genes that further induce the expression of a large battery of antiviral proteins. This antiviral program is something that must be selectively induced only when appropriate as chronic signaling is associated with severe inflammatory phenotypes and autoimmunity. These so called ‘interferonopathies’ are a clinically heterogenic group of diseases that are becoming increasingly recognized and speak to the importance of silencing the IFN-I locus in the absence of infection. Here we propose to define how a conserved gene called Kelch-Like Family Member 9 (KLHL9), which is found in the center of the IFN-I gene cluster, ensures the transcriptional repression of the region in the absence of virus infection. This proposed research will advance the understanding of how the IFN system functions at the center of immune and inflammatory diseases, and should also lead to a better understanding as to the molecular cause of at least a subset of interferonopathies.