LincR-PPP2R5C靶向调控ARNT/PP2A/STAT3和吸附miRNA介导Th2细胞分化参与支气管哮喘发生发展

哮喘是常见多发性疾病，Th2细胞在哮喘气道慢性炎症中发挥主要作用。我们应用高通量测序筛查、qRT-PCR以及FISH等方法，结合生物信息学分析，获得一条定位在胞浆中的新LncRNA，我们命名为LincR-PPP2R5C。在前期实验的基础上，申请者提出假说——（1）LincR-PPP2R5C招募ARNT，降低PPP2R5C转录，抑制PP2A/STAT3通路和Th2细胞分化；（2）LincR-PPP2R5C与ARNT结合，去除ARNT对GATA-3的抑制，促进Th2细胞分化；（3）吸附miR-132-3p和miR-148a抑制Th1/Th17细胞分化。本项目拟构建过表达或者沉默载体以及全敲除和CD4+T细胞条件性敲除小鼠，考察LincR-PPP2R5C在哮喘发生发展中介导CD4+T细胞分化的调控机制。上述研究有助于揭示LncRNA在Th2细胞相关疾病中的角色。

Th2 cells are essential in the pathogenesis of allergic asthma. We used the next-generation sequencing, qRT-PCR and FISH in the hope to get novel long non-coding RNA in the CD4+T cells in the asthma. One of novel lncRNA, located in the cytoplasma, was LincR-PPP2R5C. We hypothesize that LincR-PPP2R5C may recruit transcription factor ARNT and suppress PPP2R5C/PP2A/STAT3 signal pathway. Meanwhile, LincR-PPP2R5C may de-repress the effects of ARNT on GATA-3, the master transcription factor of Th2, and therefore boost the differentiation of Th2 cells. Besides, LincR-PPP2R5C may sponge with miR-132-3p and miR-148a, which would suppress the differentiation of Th1 and Th17 cells. We aim to clarify the above hypothesis with the gain-of-function and loss-of-function strategies in vivo and in vitro.