长链非编码RNA TINCR介导皂苷佐剂活性的作用机制研究

AJSAF系从传统中药合欢皮中筛选得到的皂苷佐剂活性有效部位，对多种畜禽商品疫苗具有显著的佐剂作用。前期研究发现，AJSAF特异性上调的长链非编码RNA——TINCR与多个核心免疫相关基因共表达，且参与AJSAF激活的ERK1/2–CREB信号通路，是AJSAF佐剂作用潜在的靶标。本项目采用TINCR过表达和敲低C2C12稳转细胞株开展获得性、缺失性功能研究以及挽救性试验，阐明TINCR在AJSAF诱导C2C12细胞炎性反应中的作用；利用组织特异性TINCR敲除小鼠，通过检测对AJSAF诱导小鼠先天性免疫和适应性免疫应答的影响，明确TINCR在介导AJSAF佐剂活性中的调控作用。旨在揭示AJSAF佐剂活性的作用机制，为研究中药免疫佐剂新靶标提供科学依据，为开发新型疫苗佐剂奠定理论基础。

The purified fraction of Albizia julibrissin saponins (AJSAF) from Cortex Albizziae is a promising adjuvant candidate for a wide spectrum of veterinary vaccines. Previous studies identified TINCR as a potential molecular target for adjuvant activity of AJSAF, basing on the co-expression of TINCR with AJSAF-induced immune response genes (IRGs) and its involvement in ERK1/2–CREB pathway. In this study, the role of TINCR in adjuvant action of AJSAF will be fully clarified. In vitro, TINCR overexpressing and knockdown C2C12 myoblasts will be used to assess the impact of TINCR on AJSAF-induced inflammatory response. And in vivo, the impact of TINCR on AJSAF-induced innate and adaptive immune responses will be assessed using tissue specific TINCR knockout mice. Therefore, the molecular mechanisms of adjuvant activity of AJSAF will be well elucidated, providing a basis for new molecular targets of adjuvant development and benefiting the rational design of effective vaccines.