Transcriptional analysis of type 1 diabetes reveals an interferon signature that precedes T cell activation

Type 1 diabetes (T1D) is an autoimmune disease triggered by T cell reactivity to protein antigens produced by the beta-cells. Here we present a chronological compendium of transcriptional profiles from islets of Langerhans isolated from non-obese diabetic (NOD) mice ranging from 2 wks up to diabetes and compared to controls. Parallel analysis was made of cellular components of the islets. Myeloid cells populated the islets early during development in all mouse strains. This was followed by a type I interferon signature detectable at 4-6 wks of age only in diabetes susceptible mice. Concurrently, CD4 T cells were found within islets, many in contact with intra-islet antigen presenting cells. Early cellular signs of islet reactivity were detected by six wks. By 8 wks, NOD islets contained all major leukocytes populations and an inflammatory gene signature. This work establishes the natural transcriptional signature of T1D and provides a resource for future research. 57 RNA samples isolated from the pancreatic islets of langerhans of experimental mice: 2-18 wk old non-obese diabetic (NOD) and newly diabetic NOD were compared to controls: NOD.RAG-/-, B6.g7 and C57BL/6. There were 3 or 6 biological replicates per condition. All mice were female. All data was normalized using RMA in Arraystar. Data table includes normalized probe intensity for every probe.1型糖尿病（Type 1 diabetes, T1D）是一种由T细胞对β细胞产生的蛋白质抗原产生免疫反应所触发的自身免疫性疾病。本研究构建了一份时序性转录组概要集，样本来自2周龄至糖尿病发病阶段的非肥胖糖尿病（non-obese diabetic, NOD）小鼠的朗格汉斯岛（islets of Langerhans），并与对照组进行比对。同时对胰岛的细胞组分开展了平行分析。髓系细胞在所有小鼠品系的胰岛发育早期即已浸润。随后仅在糖尿病易感小鼠中，可在4至6周龄时检测到I型干扰素特征信号。与此同时，胰岛内可检测到CD4阳性T细胞，其中许多与胰岛内抗原呈递细胞直接接触。至6周龄时即可检测到胰岛反应的早期细胞征象。至8周龄时，NOD小鼠胰岛已包含所有主要的白细胞群，并呈现炎症性基因表达特征。本研究明确了T1D的自然转录组特征，并为后续研究提供了宝贵的研究资源。本研究共获取57份来自实验小鼠胰腺朗格汉斯岛的RNA样本：涵盖2至18周龄的非肥胖糖尿病（NOD）小鼠及新发糖尿病NOD小鼠，并与对照组（NOD.RAG-/-、B6.g7及C57BL/6品系小鼠）进行比对。每组设置3或6次生物学重复，所有实验小鼠均为雌性。所有数据均通过Arraystar软件的RMA算法完成标准化处理。数据表格包含所有探针的标准化探针强度值。