TANK结合激酶1（TBK1）在调节Ⅰ型干扰素及NF-κB信号通路中发挥着重要作用。我们前期研究发现斑马鱼TBK1存在至少5种形式的剪接异构体，其中TBK1_tv1和TBK1_tv2负调控RLRs介导的抗病毒免疫反应，但另外3种异构体是否也参与了病原微生物感染时的免疫逃逸，以及TBK1及其剪接异构体是否调控鱼类NF-κB信号传导通路目前没有任何报道。本项目将研究TBK1及其剪接异构体在RLRs介导信号通路和NF-κB信号通路中的调控作用，比较这些剪接异构体在免疫网络调控中的异同点，将系统阐明TBK1及其剪接异构体在先天免疫应答中的功能；通过研究TBK1及其剪接异构体与信号通路接头蛋白的相互作用以及蛋白互作对病原微生物感染的影响，将全面阐明TBK1剪接异构体发挥免疫调控功能的分子机制。本项目的完成将诠释鱼类TBK1参与免疫调控的新机制，为鱼类病害防治和健康养殖提供实验和理论依据。

TANK-binding kinase 1 (TBK1) plays an important role in the regulation of type I interferon and NF-κB signaling pathways. We have found that zebrafish TBK1 has five forms of splicing isoforms, and TBK1_tv1 and TBK1_tv2 negatively regulate the RLRs-mediated antiviral immune response. However, whether the other three isoforms of TBK1 also participate in immune escape during the pathogens infection is unknown. And TBK1 and its splicing isoforms are involved in the regulation of NF-κB signaling pathway in fish has not been reported at present. This project will study the regulatory roles of TBK1 and its splicing isoforms in the RLRs- and NF-κB signaling pathway, and compare the similarities and differences of TBK1 splicing isoforms in the regulation of immune signal networks, and systematically elucidating the functions of TBK1 and its splicing isoforms in host innate immune response. And then we will not only study the interactions between TBK1 splicing isoforms and the proteins of RLRs- and NF-κB signaling pathways, but also study the influence of protein-protein interactions on pathogens infection. We will uncover the molecular mechanisms of TBK1 and its splicing isoforms in regulating the host immune response. The completion of this project will interpret the new mechanism of TBK1 involved in fish immune regulation and provide theoretical and experimental basis for fish disease prevention and healthy culture.