长链非编码RNA（lncRNA）编码的微肽在哮喘中作用未知。我们前期发现LincR-PPP2R5C的短开放阅读框架6（sORF6）可以编码微肽，促进Th2分化；体内转染sORF6后哮喘加重，2型细胞因子增多；LincR-PPP2R5C-sORF6暂命名为T细胞调控微肽（TREMP）；TREMP与哺乳动物雷帕霉素靶蛋白（mTOR）同源；TREMP过表达影响mTOR通路；质谱分析提示TREMP可结合细胞骨架相关蛋白4 (CKAP4)；CAKP4激活mTOR通路并促进IL-33分泌。我们推测：TREMP结合CAKP4调控mTOR通路、增加IL-33表达从而促进Th2分化，介导过敏性哮喘的发生发展。本项目拟构建病毒载体、全敲除和CD4+T细胞条件性敲除小鼠以及TREMP单克隆抗体等，考察TREMP在哮喘发生发展中的作用。上述研究能加深理解lncRNA的编码潜能以及CD4+T细胞在哮喘中的分化机制。

Roles of micropeptide encoded by long non-coding RNA (lncRNA) in the differentiation of CD4+T cells from allergic asthma remain largely elusive. In preliminary experiments, LincR-PPP2R5C contributed to CD4+ T cells differentiation in allergic asthma. The short Open Reading Frame 6 (sORF6) from LincR-PPP2R5C encodes a micropeptide, which regulates the T cells differentiation. We name sORF6 micropeptide TREMP (T cell regulatory micropeptide). In vitro, TREMP promotes Th2 differentiation. In vivo, TREMP aggravates asthma and type 2 cytokines in the mouse model of acute asthma. TREMP shares evolutionary similarity with mammalian target of Rapamycin (mTOR). In vitro and in vivo, TREMP over-expression affects the mTOR pathway. Mass Spectrometry analysis reveals that TREMP may interact with Cytoskeleton-associated protein 4 ( CKAP4), which activates mTOR pathway and increases IL-33 secretion. Therefore, we postulate the hypothesis that LincR-PPP2R5C encodes micropeptide TREMP may regulate the Th2 differentiation via CKAP4-mTOR-IL-33 in allergic asthma. To explore the above hypothesis, we would (1) construct lentivirus system, which aims to over-expressing or silencing TREMP in the CD4+ T cells; (2) knockout TREMP in the mouse or conditionally knockout TREMP in the CD4+ T cells in vivo; (3) produce TREMP monoclonal antibody and test its function in the CD4+T cells differentiation and asthma. Our work would of great value in the exploring the roles of lncRNA encodes novel micropeptide in the differentiation of CD4+ T cells in allergic asthma.