Enhanced T cell responses to IL-6 in type 1 diabetes are associated with early clinical disease and increased IL-6 receptor expression

IL-6 is a proinflammatory cytokine implicated in multiple autoimmune diseases. Here we show that IL-6 induced STAT3 and STAT1 phosphorylation is enhanced in CD4 and CD8 T cells from patients with T1D compared to healthy controls. Enhanced IL-6/pSTAT3 is associated with increased surface IL-6R and early clinical disease. The transcriptome of IL-6 treated CD4 T cells from T1D patients reveals upregulation of genes involved in T cell migration. The data suggest that individuals with type 1 diabetes may benefit from therapeutic targeting of the IL-6 pathway. Overall design: CD4+CD25- T cells were purified from thawed PBMC of seven subjects with type 1 diabetes. Cells were left unstimulated or were treated with 10ng/ml IL-6 for 24 hours. RNA was extracted and RNA sequencing was performed.

白细胞介素6（Interleukin-6, IL-6）是一种促炎性细胞因子，与多种自身免疫性疾病密切相关。本研究发现，与健康对照相比，1型糖尿病（Type 1 Diabetes, T1D）患者的CD4及CD8 T细胞中，IL-6诱导的信号转导与转录激活因子3（Signal Transducer and Activator of Transcription 3, STAT3）和信号转导与转录激活因子1（Signal Transducer and Activator of Transcription 1, STAT1）磷酸化水平显著升高。升高的IL-6/pSTAT3信号通路与细胞表面IL-6受体表达增加及疾病早期临床表型相关。对1型糖尿病患者的CD4 T细胞经IL-6处理后的转录组分析显示，参与T细胞迁移的基因表达显著上调。本研究数据表明，1型糖尿病患者或可从IL-6通路靶向治疗中获益。
实验整体设计：从7名1型糖尿病患者的冻存外周血单个核细胞（peripheral blood mononuclear cell, PBMC）中纯化得到CD4+CD25- T细胞，将细胞分为未刺激对照组与10ng/ml IL-6处理24小时组，随后提取RNA并进行RNA测序（RNA sequencing, RNA-seq）。