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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：
8383094
负责人：
Qijing Li
金额：
$ 35.94万
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 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8383094
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 Functional RNA 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 Virus autoreactive T cell base combat immunoregulation in vivo inhibitor/antagonist loss of function member neoplastic cell nervous system disorder neuron development novel novel therapeutics overexpression response scaffold

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）：miR-19b的调节机制，一种新的T细胞自身免疫介质：CD4 T细胞的不适当激活和分化引发并协调了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开发治疗这些疾病的新疗法具有直接意义。虽然基于蛋白质的T细胞抗原识别下游信号转导机制已经被彻底研究，但我们最近意识到一个新的和关键的因素决定T细胞命运- 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经得到了很好的证实。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主要通过簇中mir-19b成分的活性，决定了CD4 T细胞介导的自身免疫的进展。我们的目标是发现miR-19b支持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。