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

项目总结 I型干扰素(IFN-I)是抵御病毒的第一道防线，在协调 先天和获得性免疫反应。传染性病毒的存在引发了一连串的事件 导致干扰素-I基因的激活，从而进一步诱导大量抗病毒蛋白的表达。 只有在适当的情况下，才能有选择地诱导这种抗病毒方案 信号转导与严重炎症表型和自身免疫有关。这些所谓的 干扰素病是一组临床上异质性的疾病，人们越来越多地认识到这种疾病 并谈到在没有感染的情况下沉默干扰素-I基因的重要性。在此，我们建议 定义一个被称为Kelch-like Family Members 9(KLHL9)的保守基因是如何发现的，它位于 干扰素-I基因簇，确保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干扰素系统如何在免疫中心发挥作用的理解 和炎症性疾病，也应该有助于更好地理解AT的分子原因 至少是干扰素病的一个子集。

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.