lncRNA ENST00000445003.1通过Oct-1调控变应性鼻炎CD4+T细胞分化的机制研究

CD4+T细胞分化偏移造成的免疫失衡是变应性鼻炎(AR)发病的核心机制，长链非编码RNA(lncRNA)与AR的发病显著相关，有研究表明lncRNA可协同转录因子调节CD4+T细胞分化促进变应性气道炎症发生，但其具体作用机制尚不清楚。我们前期研究发现以ENST00000445003.1为代表的lncRNA在AR中显著高表达并与CD4+T细胞分化相关转录因子Oct-1共价结合，干扰目的lncRNA可显著抑制Th2细胞分化及相关细胞因子表达。因此我们提出科学假设：目的lncRNA通过招募Oct-1调节CD4+T细胞的分化，促进AR发生。本项目拟通过细胞实验及AR小鼠模型初步阐明目的lncRNA通过Oct-1对CD4+T分化的调控作用及分子机制；利用临床标本及临床资料分析目的lncRNA与变应性鼻炎发生发展的关系。从lncRNA角度诠释AR的发病机制，为AR的诊断及治疗提供理论依据及分子靶点。

Immune imbalance caused by CD4+T cell differentiation migration is the core mechanism of allergic rhinitis (AR). Long chain non-coding RNA (lncRNA) is significantly correlated with the incidence of AR. Some studies have shown that lncRNA can coordinate with transcription factors to regulate CD4+T cell differentiation and promote allergic airway inflammation, but its specific mechanism of action is still unclear. Our previous study found that lncRNA represented by ENST00000445003.1 was significantly highly expressed in AR and covalently bound to oct-1, a transcription factor related to CD4+T cell differentiation. Interference with lncRNA expression can significantly inhibit Th2 cell differentiation and expression of related cytokines. Therefore, we propose a scientific hypothesis: Target lncRNA regulates the differentiation and function of CD4+T cells by recruiting oct-1, and promotes the occurrence of AR. This project intends to preliminarily elucidate the regulatory mechanism of lncRNA on CD4+T differentiation through cell experiments and AR mouse models, and further clarify the relationship between lncRNA and the development of allergic rhinitis. The pathogenesis of AR will be interpreted from the perspective of lncRNA to provide theoretical basis and molecular target for the diagnosis and treatment of AR.