| 项目编号 | PRJCA009531 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 项目标题 | LARP4 is a checkpoint regulator of for naive CD4+ T cell quiescence and quiescence exit | ||||||||
| 涉及领域 | Medical | ||||||||
| 数据类型 |
Epigenomics
Raw sequence reads Genome sequencing Single cell sequencing |
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| 物种名称 | Mus musculus | ||||||||
| 描述信息 | Naive T cells maintain a quiescent state and exit from quiescence after antigen stimulation, but the underlying molecular mechanisms remain largely unknown. Here, we identify RNA binding protein LARP4 as an important regulator responsible for naive CD4+ T cell quiescence and quiescence exit. LARP4-deficient naive CD4+ T cells show an enforced quiescent state and decreased quiescence exit due to a significant change in T cell quiescence and activation related messenger RNA (mRNA) abundance, which increases the threshold to activation of naive CD4+ T cells. Mechanistically, LARP4 deficiency leads to a decrease in mRNA stability of certain LARP4-binding targets especially for T cell activation associated genes, which dampens quiescence exit of naive CD4+ T cells. Moreover, CD4+ helper T cell subsets differentiation were also been impaired after LARP4 knock out, contributing to ameliorating autoimmune and allergic diseases. More interestingly, we designed MLLE mimic 22-aa peptidesmall molecular peptide, named as LIPEP, and its treatment could perfectly mimic the deficiency of LARP4 and lighten autoimmune and allergic disease. Our study reveals a key mechanism underlying naive CD4+ T cell quiescence and quiescence exit and suggests that LARP4-dependent control of T cell quiescence and quiescence exit is a crucial for maintaining T cell homeostasis to facilitate adaptive immune function and a potential target of autoimmune and allergic diseases. | ||||||||
| 样品范围 | Multiisolate | ||||||||
| 发布日期 | 2025-06-16 | ||||||||
| 项目资金来源 |
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| 提交者 | Yi Tian (tianyi19831015@hotmail.com) | ||||||||
| 提交单位 | Third Military Medical University(Army Medical University) | ||||||||
| 提交日期 | 2022-05-11 |