Regulatory mechanisms of miR-19b, a novel mediator of T cell autoimmunity

描述(由申请人提供)：一种新的T细胞自身免疫介体miR-19b的调节机制：CD4T细胞的不适当激活和分化导致并协调了一系列自身免疫性疾病的发生和发展。了解CD4T细胞的内在调节机制对开发治疗这些疾病的新疗法具有直接意义。虽然T细胞抗原识别下游基于蛋白质的信号转导机制已经被深入研究，但我们最近意识到决定T细胞命运的一个新的关键元件-microRNA(MiRNA)。MiR-17-92是一个编码六种不同miRNAs的基因簇，其在肿瘤细胞中的重要内在作用已被证实。然而，我们最近发现，mir-17-92簇也以T细胞固有的方式增强抗肿瘤免疫。此外，我们的初步研究表明，mir-17-92决定了CD4T细胞介导的自身免疫的进展，主要是通过该簇的mir-19b成分的活性。我们的目标是发现miR-19b促自身免疫调节功能的分子机制，从而建立miR-19b作为治疗自身免疫性疾病的潜在靶点。

DESCRIPTION (provided by applicant): Regulatory mechanisms of miR-19b, a novel mediator of T cell autoimmunity: The inappropriate activation and differentiation of CD4 T cells elicits and orchestrates the onset and progression of a wide range of autoimmune diseases. Understanding CD4 T cells' intrinsic regulatory mechanisms has direct implications for the development of novel therapeutics to treat these diseases. While the protein-based signal transduction machinery downstream of T cell antigen recognition has been thoroughly studied, we have recently become aware of a novel and crucial element dictating T cell fate-microRNA (miRNA). mir-17-92 is a gene cluster encoding six different miRNAs, whose important tumor-cell-intrinsic roles in cancer have been well established. However, we have recently discovered that the mir-17-92 cluster also potentiates anti-tumor immunity in a T-cell-intrinsic manner. Furthermore, our preliminary studies indicate that mir-17-92 dictates the progression of CD4 T cell-mediated autoimmunity, principally through the activity of the cluster's mir-19b component. We aim to discover the molecular mechanism underpinning miR-19b's pro- autoimmune regulatory function, and thereby to establish miR-19b as a potential target for therapy of autoimmune diseases.