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Translational Reprogramming by Regulatory T Cells

Translational Reprogramming by Regulatory T Cells
调节性 T 细胞的翻译重编程
批准号:
9765776
负责人:
Ram Savan
金额:
$27.29万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-01-04 至 2020-12-31

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中文摘要
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英文摘要
Project Summary Regulatory T cells (Tregs) play an indispensable role in maintaining immunological tolerance to self-antigens and in suppressing excessive immune responses deleterious to the host by exerting a suppressive program towards a wide variety of target immune cells. However, the intracellular molecular events that mediate such suppression in target cells in still poorly understood. In this study, we will investigate the molecular nature of this suppression program with the central hypothesis that regulation of the translational machinery and specific mRNA translation control is at the core of this reprogramming event. We will utilize a novel genetic tool that allows immunopurification of ribosomes in virtually any immune cell type in both in vitro and in vivo immune models called ‘RiboTag.’ Using RiboTag, we will capture the genome-wide translatome (all mRNAs being translated in time and space) during Treg-dependent immunological tolerance breakdown. We will further investigate the mechanism of such mRNA transcript-specific translation control with the hypothesis that the trans-acting translation regulatory protein factors are modulated in target cells encountered by Tregs. The RiboTag mediated immunopurification of ribosomes followed by mass spectrometry based proteomics will delineate such changes in the riboproteome (the ribosome itself or ribosome-associated factors) endowed by Treg encounter in target cells. These studies will break new ground in understanding a novel layer of gene expression control imposed by Tregs, a critical component in our immune system essential for immunological tolerance.
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