Department of Pediatric Hematology/Oncology, Dr von Haunersches Kinderspital, Munich, Germany.
1] Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany [2] Immune-Monitoring and Clinical Cooperation Groups 'Antigen-specific Immunotherapy', Helmholtz Center Munich (Neuherberg), Munich, Germany.
Genes Immun. 2014 Jul-Aug;15(5):303-12. doi: 10.1038/gene.2014.20. Epub 2014 May 22.
Owing to their manifold immune regulatory functions, regulatory T cells (Treg) have received tremendous interest as targets for therapeutic intervention of diverse immunological pathologies or cancer. Directed manipulation of Treg will only be achievable with extensive knowledge about the intrinsic programs that define their regulatory function. We simultaneously analyzed miR and mRNA transcript levels in resting and activated human Treg cells in comparison with non-regulatory conventional T cells (Tcon). Based on experimentally validated miR-target information, both transcript levels were integrated into a comprehensive pathway analysis. This strategy revealed characteristic signal transduction pathways involved in Treg biology such as T-cell receptor-, Toll-like receptor-, transforming growth factor-β-, JAK/STAT (Janus kinase/signal transducers and activators of transcription)- and mammalian target of rapamycin signaling, and allowed for the prediction of specific pathway activities on the basis of miR and mRNA transcript levels in a probabilistic manner. These data encourage new concepts for targeted control of Treg cell effector functions.
由于其多样的免疫调节功能，调节性 T 细胞（Treg）作为治疗多种免疫病理学或癌症的靶点受到了极大的关注。只有对决定其调节功能的内在程序有了广泛的了解，才能对 Treg 进行定向操作。我们同时分析了静息和激活的人 Treg 细胞与非调节性常规 T 细胞（Tcon）中的 miR 和 mRNA 转录水平。基于经过实验验证的 miR-靶信息，将两个转录水平整合到一个综合的途径分析中。该策略揭示了涉及 Treg 生物学的特征信号转导途径，如 T 细胞受体、Toll 样受体、转化生长因子-β、JAK/STAT（Janus kinase/signal transducers and activators of transcription）和哺乳动物雷帕霉素靶蛋白信号通路，并允许基于 miR 和 mRNA 转录水平以概率方式预测特定途径的活性。这些数据为靶向控制 Treg 细胞效应功能提供了新的概念。
