大黄鱼白细胞介素4/13A激活的信号通路及其调控机制研究

哺乳类IL-4和IL-13主要通过激活JAK-STAT、PI3K/Akt和Ras/ERK通路介导Th2免疫应答，且其激活的通路受SOCS1和特定miRNA调控。但目前对鱼类IL-4/13信号通路及其调控机制知之甚少。前期我们完成了大黄鱼IL-4/13A的功能研究，本项目拟在此基础上鉴定大黄鱼IL-4/13A的受体及下游接头分子，研究其对JAK-STAT、PI3K/Akt和Ras/ERK通路的激活作用，以揭示大黄鱼IL-4/13A激活的信号通路；通过研究SOCS1和靶向IL-4/13A及其受体的miRNA对IL-4/13A信号通路活化的调节作用，确定SOCS1阻断的靶蛋白及其功能域，以及miRNA的靶基因，从SOCS蛋白阻断和miRNA转录后调控两个层次阐明大黄鱼IL-4/13A通路的调控机制。预期结果对认识鱼类IL-4/13信号通路及调控机制具有重要意义，也为大黄鱼病害免疫防治提供新思路。

Mammalian interleukin (IL)-4 and IL-13 mediate their effects on Th2 (T-helper cell type 2) response by activating JAK-STAT, PI3K/Akt and Ras/ERK pathways. The suppressor of cytokine signaling 1 (SOCS1) and some miRNAs play important roles in regulation of these pathways. However, currently little is known about the signaling pathways and their regulatory mechanisms of IL-4/13 in bony fish. In the previous study, the function of large yellow croaker (Larimichthys crocea) IL-4/13A (LcIL-4/13A) has been characterized. The potential receptor subunits and related signaling genes were also found in large yellow croaker. In this project, the specific receptors, adaptor molecules, and the effects of LcIL-4/13A on activation of JAK-STAT, PI3K/Akt and Ras/ERK pathways will be further investigated to determine the signaling pathways that are activated by LcIL-4/13A. The regulating effects of SOCS1 and miRNAs on activation of JAK-STAT, PI3K/Akt and Ras/ERK pathways by LcIL-4/13A, the target proteins of SOCS1, and the target genes of miRNAs also will be investigated, revealing the regulatory mechanisms of LcIL-4/13A signal pathways. These results will help to understand the signaling pathways and their regulatory mechanisms of fish IL-4/13, and also provide new ideas for disease prevention of large yellow croaker.