Funktionelle Differenzierung und Plastizität humaner Th17 Zellen

产生IL-17的T辅助细胞(Th17细胞)最近作为一种新的T细胞亚群出现，在微生物防御和自身免疫性疾病中发挥作用。驱动人类Th17谱系规范的细胞和分子因素尚未完全阐明，鉴于已报道的与小鼠系统的差异，仍存在很大争议。T细胞受体信号的强度和持续时间、抗原剂量或共刺激类型能够调节Th1和Th2反应，但尚未在Th17细胞中进行研究。MicroRNAs越来越被认为是细胞命运的重要决定因素，并可能像转录因子一样，对Th17细胞亚群的功能分化做出贡献。因此，目的将是在细胞和分子水平上破译Th17细胞承诺的要求。有关Th17细胞谱系维持的问题将通过研究这种新的T辅助细胞亚群的可塑性来解决。这项研究将为启动自身免疫的事件提供洞察力，可能为免疫接种策略产生新的治疗靶点。

T helper cells that produce IL-17 (Th17 cells) have recently emerged as a new T cell subset with roles in microbial defense and autoimmune diseases. The cellular and molecular factors driving human Th17 lineage specification have not been fully elucidated and remain highly controversial in light of reported discrepancies with the murine system. Strength and duration of T cell receptor signaling, antigen dose or type of co-stimulation are able to modulate Th1 and Th2 responses but have not been investigated in Th17 cells. MicroRNAs are increasingly recognized as important determinants of cell fate specification and might, like transcription factors, contribute to the functional differentiation of the Th17 cell subset. Therefore the aim will be to decipher the requirements for Th17 cell commitment at a cellular and molecular level. Questions related to Th17 cell lineage maintenance will be addressed by studying the plasticity of this new T helper cell subset. This study will provide insights into the events initiating autoimmunity, potentially yielding novel therapeutic targets for immune vaccination strategies.