Determining the mechanisms by which a circular RNA regulates the function of Th17 cells

确定环状 RNA 调节 Th17 细胞功能的机制

基本信息

  • 批准号:
    10814585
  • 负责人:
  • 金额:
    $ 21.13万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-05-12 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT There is no cure for autoimmune diseases, which affect more than 23 million Americans. IL-17-producing T helper cells (Th17 cells) play a major role in the pathogenesis of autoimmune diseases. Investigating regulatory mechanisms for Th17 differentiation and function will provide new opportunities for therapeutics. Circular RNAs (circRNAs), whose functions are previously underestimated, have great potential in various cellular activities from different types of cells. However, the role of circRNAs in Th17 cells is poorly understood. Herein, a circRNA produced from the precursor mRNA for Usp3 (circUsp3) was found to be essential for Th17 cell function. Our long-term goal is to develop therapeutically useful Th17 inhibitors for the clinical treatment of human autoimmune diseases. Our overall objectives in this application are to elucidate the molecular mechanisms by which circUsp3 provokes Th17 functions. The central hypothesis is that circUsp3 elevates Th17 differentiation in vitro and promotes Th17-mediated autoimmunity in vivo through forming complex with RORγt. The rationale for this project is that determination of the essential roles of circUsp3 in Th17 function is likely to provide proof- of-concept that circRNA can be targeted to therapeutically treat autoimmune diseases. The central hypothesis will be tested by pursuing two specific aims: 1) Determine the requirement of circUsp3-RORγt complex in Th17 function; and 2) Determine the mechanisms by which circUsp3 activates RORγt-mediated transcription. Upon conclusion, we will understand the role for circUsp3 in Th17 function. These results are expected to have an important positive impact because they will provide a strong evidence base of critical roles of previously unrecognized circRNA-based regulatory mechanisms for Th17 function, ultimately providing opportunities for the development of novel therapies to treat autoimmune diseases. The proposed research is innovative because we investigate the effect of a circular RNA in Th17 function, a heretofore-unexamined process. Since circRNAs are broadly expressed in immune cells, this study will open a new era for exploring regulatory mechanisms of immune responses.
项目总结/文摘

项目成果

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Zhiheng He其他文献

Zhiheng He的其他文献

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{{ truncateString('Zhiheng He', 18)}}的其他基金

Distinguishing inflammatory Th17 subsets through using an autoimmune Th17-selective inhibitor
通过使用自身免疫 Th17 选择性抑制剂区分炎症 Th17 亚群
  • 批准号:
    10527102
  • 财政年份:
    2022
  • 资助金额:
    $ 21.13万
  • 项目类别:
Determining the mechanisms by which a circular RNA regulates the function of Th17 cells
确定环状 RNA 调节 Th17 细胞功能的机制
  • 批准号:
    10509244
  • 财政年份:
    2022
  • 资助金额:
    $ 21.13万
  • 项目类别:
Distinguishing inflammatory Th17 subsets through using an autoimmune Th17-selective inhibitor
通过使用自身免疫 Th17 选择性抑制剂区分炎症 Th17 亚群
  • 批准号:
    10814571
  • 财政年份:
    2022
  • 资助金额:
    $ 21.13万
  • 项目类别:
Dissecting functions of IL-23-dependent inflammatory Th17 cells
解析 IL-23 依赖性炎症 Th17 细胞的功能
  • 批准号:
    10815237
  • 财政年份:
    2022
  • 资助金额:
    $ 21.13万
  • 项目类别:
Dissecting functions of IL-23-dependent inflammatory Th17 cells
解析 IL-23 依赖性炎症 Th17 细胞的功能
  • 批准号:
    10566390
  • 财政年份:
    2022
  • 资助金额:
    $ 21.13万
  • 项目类别:

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