Functional Analysis of MicroRNAs in Lymphocyte Development and Immune Tolerance

MicroRNA 在淋巴细胞发育和免疫耐受中的功能分析

• 批准号: 8512652
• 负责人: Changchun Xiao
• 金额: $ 29.13万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-21 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8512652
• 关键词: Address; Apoptosis; Autoimmune Diseases; B-Cell Development; B-Lymphocytes; Biological Process; Bone Marrow; Cell Differentiation process; Code; Development; Diagnostic; Exhibits; Expression Library; Future; Gene Targeting; Genes; Genetic; Goals; Immune Tolerance; Immune system; Immunotherapy; Individual; Lead; Lymphocyte; Malignant Neoplasms; Mammals; Messenger RNA; MicroRNAs; Molecular; Molecular Mechanisms of Action; Nature; Organ Transplantation; Pattern; Play; Porifera; Proteins; Publishing; Research; Role; Sequence Analysis; Small RNA; Surface; Technology; Therapeutic Intervention; Tissues; Transgenic Mice; Untranslated Regions; anti-IgM; deep sequencing; loss of function; mouse model; protein expression; reconstitution; research study; screening; therapeutic target

DESCRIPTION (provided by applicant): MicroRNAs (miRNAs) have recently emerged as a major class of trans-factors that regulate expression of protein coding genes at the mRNA level, thereby controlling a diverse range of biological processes including cell differentiation, proliferation, and apoptosis. Genetic studies from us and other groups have demonstrated that miRNAs are involved in the control of lymphocyte development and function, as well as in autoimmune diseases. However, the specific functions of individual miRNAs in the immune system remain largely unknown. We propose to use a newly developed lentiviral miRNA expression library, the recently published miRNA sponge technology, and a unique mouse model of B cell tolerance to systematically assess the functions of miRNAs in B cell development and tolerance. The primary goal of this proposal is to identify miRNAs that play important roles in B cell development and tolerance and, by doing so, to open up new avenues for in-depth studies of specific functions and molecular mechanisms of individual miRNAs in the future.

描述（由申请人提供）：微小RNA（miRNAs）最近已经成为在mRNA水平上调节蛋白质编码基因表达的主要类别的反式因子，从而控制多种生物过程，包括细胞分化、增殖和凋亡。我们和其他研究小组的遗传学研究表明，miRNAs参与控制淋巴细胞的发育和功能，以及自身免疫性疾病。然而，单个miRNAs在免疫系统中的具体功能在很大程度上仍然未知。我们建议使用一个新开发的慢病毒miRNA表达文库，最近公布的miRNA海绵技术，和一个独特的小鼠模型的B细胞的耐受性，以系统地评估的功能的miRNA在B细胞的发展和耐受性。本研究的主要目的是鉴定在B细胞发育和耐受中发挥重要作用的miRNAs，为今后深入研究miRNAs的功能和分子机制开辟新的途径。