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

T细胞自身免疫的新型介质miR-19b的调节机制

基本信息

批准号：
8969661
负责人：
Qijing Li
金额：
$ 38.1万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-01 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8969661
关键词：
Acute Antigens Autoimmune Diseases Autoimmune Process Autoimmunity Biochemical Biology Brain CD4 Positive T Lymphocytes Cell Lineage Cells Cellular biology Cessation of life Chemical Engineering Complex Cytokine Signaling Data Development Disease Elements Engineering Enhancers Epigenetic Process Etiology Gene Cluster Genes Goals Human Immune Immune response Immune system Immunotherapy In Vitro Individual Inflammation Inflammatory Response Interleukin-17 Knowledge Link Lymphoid Maintenance Major Histocompatibility Complex Malignant Neoplasms Mediating Mediator of activation protein Membrane Methyl-CpG-Binding Protein 2 MicroRNAs Molecular Mutation Nature Oligonucleotides Organ Pathway interactions Pattern Peptides Phase Phosphoric Monoester Hydrolases Phosphotransferases Physiological Play Process Production Proteins Receptor Activation Regulation Research Personnel Rett Syndrome Role Signal Pathway Signal Transduction Staging T cell response T-Cell Activation T-Cell Receptor T-Lymphocyte Th1 Cells Therapeutic Intervention Tumor Immunity Uncertainty Untranslated RNA Virus autoreactive T cell base combat epigenetic regulation immunoregulation in vivo inhibitor/antagonist loss of function member neoplastic cell nervous system disorder neuron development novel novel therapeutics overexpression response scaffold targeted treatment

项目摘要

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.

描述（由申请人提供）：T 细胞自身免疫的新型介质 miR-19b 的调节机制：CD4 T 细胞的不当激活和分化会引发并协调多种自身免疫性疾病的发生和进展。了解 CD4 T 细胞的内在调节机制对于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得到深入研究，但我们最近意识到一种决定 T 细胞命运的新颖且关键的元素——microRNA (miRNA)。 mir-17-92 是一个编码六种不同 miRNA 的基因簇，其在癌症中重要的肿瘤细胞内在作用已得到充分证实。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 主要通过簇的 mir-19b 成分的活性来决定 CD4 T 细胞介导的自身免疫的进展。我们的目标是发现支持 miR-19b 促自身免疫调节功能的分子机制，从而将 miR-19b 确立为治疗自身免疫性疾病的潜在靶点。