非经典NF-kappaB信号途径不仅促进淋巴器官形成、B细胞发育与成熟，对T细胞、树突状细胞、巨噬细胞等其他免疫细胞的活化与功能也具有重要的调节作用。对于非经典NF-kappaB信号途径的研究越来越受到重视，但其功能与调控机制远未阐明。我们在前期工作中发现泛素连接酶Nedd4l可促进非经典NF-kappaB信号途径重要的调控分子TRAF3的泛素化，Nedd4l缺失抑制LPS、CD40L诱导的非经典NF-kappaB信号途径的活化，推测Nedd4l可能是一个新的非经典NF-kappaB信号途径调节分子。本课题将进一步研究Nedd4l和非经典NF-kappaB信号分子间的相互作用，揭示非经典NF-kappaB信号途径调控的新机制，为非经典NF-kappaB信号途径相关的免疫干预提供新的靶点。

The study of regulation of non-canonical NF-kappaB is of great importance and attaches more and more attention.However,the mechanism regulating non-canonical NF-kappaB remains unilluminated.Our primary results demonstrate that E3 ligase Nedd4l promotes TRAF3 polyubiquitination and Nedd4l deficiency inhibits LPS and CD40L-induced activation of non-canonical NF-kappaB pathway, indicating that Nedd4l is a novel regulator of non-canonical NF-kappaB pathway. The project will illuminate the mechanism by which Nedd4l regulates non-canonical NF-kappaB pathway, providing new target for immunotherapy for diseases associated with activation of non-canonical NF-kappaB pathway.