Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
Blood. 2012 Jun 7;119(23):e151-60. doi: 10.1182/blood-2012-01-407528. Epub 2012 Apr 27.
Th17 cells play an essential role in the pathogenesis of autoimmune and inflammatory diseases. Most of our current understanding on Th17 cell differentiation relies on studies carried out in mice, whereas the molecular mechanisms controlling human Th17 cell differentiation are less well defined. In this study, we identified gene expression changes characterizing early stages of human Th17 cell differentiation through genome-wide gene expression profiling. CD4(+) cells isolated from umbilical cord blood were used to determine detailed kinetics of gene expression after initiation of Th17 differentiation with IL1β, IL6, and TGFβ. The differential expression of selected candidate genes was further validated at protein level and analyzed for specificity in initiation of Th17 compared with initiation of other Th subsets, namely Th1, Th2, and iTreg. This first genome-wide profiling of transcriptomics during the induction of human Th17 differentiation provides a starting point for defining gene regulatory networks and identifying new candidates regulating Th17 differentiation in humans.
Th17 细胞在自身免疫性和炎症性疾病的发病机制中起关键作用。我们目前对 Th17 细胞分化的大部分了解都依赖于在小鼠中进行的研究，而控制人类 Th17 细胞分化的分子机制则定义得不够明确。在这项研究中，我们通过全基因组基因表达谱分析鉴定了表征人类 Th17 细胞分化早期阶段的基因表达变化。我们从脐血中分离出 CD4+细胞，然后用 IL1β、IL6 和 TGFβ 启动 Th17 分化，以确定起始 Th17 分化后基因表达的详细动力学。在蛋白质水平上进一步验证了选定候选基因的差异表达，并分析了其在起始 Th17 分化与起始其他 Th 细胞亚群（即 Th1、Th2 和 iTreg）的特异性。这是首次对人类 Th17 分化诱导过程中的转录组学进行全基因组分析，为定义基因调控网络和识别新的候选基因调节人类 Th17 分化提供了起点。
