LncRNATUG1 Facilitates Th2 Cell Differentiation by Targeting the miR-29c/B7-H3 Axis on Macrophages.
LncRNATUG1 Facilitates Th2 Cell Differentiation by Targeting the miR-29c/B7-H3 Axis on Macrophages.
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LncRNATUG1 通过靶向巨噬细胞上的 miR-29c/B7-H3 轴促进 Th2 细胞分化
DOI：
10.3389/fimmu.2021.631450
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发表时间：
2021
影响因子：
7.3
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Sun H;Wang T;Zhang W;Dong H;Gu W;Huang L;Yan Y;Zhu C;Chen Z
长非编码RNA(LncRNA)在哮喘中的作用尚不清楚。在这项研究中，我们研究了长非编码RNA牛磺酸上调1(LncRNA TUG1)在哮喘中的作用。我们发现，LncRNA TUG1是哮喘患儿单核细胞中差异表达的LncRNAs之一，与Th细胞分化有关。LncRNA、TUG1和miR-29c主要分布在巨噬细胞的胞浆中。我们的数据表明，屋尘螨刺激的巨噬细胞中的lncRNA TUG1以剂量依赖的方式增加。利用功能得失策略，我们发现miR-29c可能通过直接靶向共刺激分子B7-H3来调节Th2细胞的分化。此外，下调lncRNA TUG1可降低CD4+T细胞中GATA3的水平，并与miR-29c/B7-H3轴相关。此外，双荧光素酶报告实验证实，lncRNA TUG1作为竞争内源RNA与miR-29c结合。根据挽救实验，lncRNA TUG1通过miR-29c调节Th2细胞的分化。这些数据表明，巨噬细胞中的lncRNA TUG1通过miR-29c/B7-H3轴调节Th2细胞的分化。
The role of long non-coding RNAs (lncRNA) in asthma remains unclear. In this study, we examined the role of long non-coding RNA taurine upregulated 1 (lncRNA TUG1) in asthma. We found that lncRNA TUG1 is one of the differentially expressed lncRNAs in the monocytes of asthmatic children and is associated with Th cell differentiation. LncRNA TUG1 and miR-29c are mainly distributed in the cytoplasm of macrophages. Our data suggested that lncRNA TUG1 increased in macrophages stimulated by House Dust Mite in a dose-dependent manner. Using loss- and gain of function strategy, we found that miR-29c might regulate Th2 cell differentiation by directly targeting co-stimulatory molecule B7-H3. Furthermore, down-regulation of lncRNA TUG1 decreased the level of GATA3 in CD4+T cells and was associated with miR-29c/B7-H3 axis. Moreover, the dual-luciferase reporter assay confirmed that lncRNA TUG1 serves as a competing endogenous RNA to sponge miR-29c. According to the rescue experiment, lncRNA TUG1 regulated Th2 cell differentiation via miR-29c. These data suggest that lncRNA TUG1 in macrophages regulates Th2 cell differentiation via miR-29c/B7-H3 axis.
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