长非编码RNA LIRIL2R通过调节IL2RA调节人体CD4+调节T细胞的FOXP3水平和抑制功能
Syed Bilal Ahmad Andrabi1,2, Ubaid Ullah Kalim1,2, Senthil Palani1
1Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland.
概括
一种新发现的长跨基因非编码RNA,LIRIL2R,对于调节人类调节性T细胞 (Treg) 功能至关重要. LIRIL2R控制IL2RA表达和Treg特异性基因活性,影响免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 调节性T细胞 (Tregs) 对免疫平衡至关重要,它们的功能障碍与自身免疫和癌症有关.
- 人类Treg发育和功能的表观遗传调节仍然不完全理解.
- 长跨基因非编码RNAs (lincRNAs) 在表观遗传调节中发挥作用.
研究的目的:
- 识别和表征一种涉及人类Treg分化和功能的新型lincRNA.
- 为了阐明这种lincRNA调节互白素-2受体α (IL2RA) 基因的机制.
- 研究这种lincRNA对Treg特定基因表达和抑制能力的影响.
主要方法:
- 鉴定了一种在人类Treg分化过程中上调的新型lincRNA (LIRIL2R).
- 对LIRIL2R缺乏Tregs的转录组学,表观组学和蛋白质组学分析.
- 通过RNA净化分离染色体,然后进行测序 (ChIRP-seq) 以映射LIRIL2R结合部位.
- 在IL2RA位点的LIRIL2R结合区域的CRISPR介导删除.
主要成果:
- 鉴定出 LIRIL2R 是 IL2RA 位点上游结合的核链接RNA,调节其表观遗传景观和转录.
- 通过CRISPR介导的LIRIL2R结合部位的删除减少了IL2RA表达.
- LIRIL2R缺乏导致Treg签名基因 (FOXP3,CTLA4,PDCD1) 的表达减少,T细胞效应基因 (SATB1,GATA3) 的表达增加.
- 失去LIRIL2R导致受Treg介导的抑制受损.
结论:
- LIRIL2R是人类Treg发育和功能的关键表观遗传调节剂.
- LIRIL2R通过调节IL2RA和其他特异性Treg基因来控制Treg标识和抑制功能.
- LIRIL2R代表了免疫相关疾病的潜在治疗标.
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