MAPK/ERK通路调控尼罗罗非鱼T细胞免疫的分子机制

作为信号转导的枢纽，MAPK/ERK通路在T细胞诸多的免疫生物学过程中发挥着至关重要的调控作用。然而，该通路对低等脊椎动物T细胞免疫的调控机制仍不清楚。课题组前期工作以硬骨鱼尼罗罗非鱼为对象，建立了其T细胞研究平台；发现了尼罗罗非鱼具有保守的MAPK/ERK通路，证明了该通路参与尼罗罗非鱼抵御病原感染的适应性免疫应答，参与并调控尼罗罗非鱼T细胞的激活过程。在此基础上，本项目拟综合运用细胞生物学、分子与细胞免疫学、生物化学等技术，搭建尼罗罗非鱼MAPK/ERK信号通路，探讨其激活模式；解析该通路对尼罗罗非鱼T细胞激活、增殖以及感染清除的调控机制；同时，分析MAPK/ERK通路调控T细胞激活的转录特性，并揭示通路下游转录因子对IL-2等T细胞免疫重要基因的转录调控机制。研究成果将从全新的视角揭示硬骨鱼适应性免疫的调控机制，也为鱼类养殖的病害防治提供新思路。

As a junction of signal transduction, MAPK/ERK signaling pathway plays an important role in many immune processes of T cells. However, the regulatory mechanism of this pathway in T cell immunity of lower vertebrates is still unclear. In previous study, we have constructed a T cell research platform for the teleost Nile tilapia (Oreochromis niloticus), and revealed that Nile tilapia employed an evolutionary conserved MAPK/ERK pathway to regulate the anti-bacterial adaptive immune response via controlling T cell activation. Based on these results, using technologies of cellular biology, biochemistry, molecular and cellular immunology, we will construct the whole MAPK/ERK pathway of Nile tilapia and reveal its activation pattern in this present project. After that, we will investigate the regulatory mechanism of MAPK/ERK pathway in activation, proliferation and function of Nile tilapia T cells. Meanwhile, the transcriptional mechanism of transcription factors that downstream of MAPK/ERK pathway to the important genes of T cells, such as IL-2, will be investigated after the transcriptional properties of this pathway on T cell activation are analyzed by RNA sequencing. Results of this project will reveal the mechanism of adaptive immunity in teleost from a new perspective, and provide new ideas for disease control of fish farming.