扇贝胆碱能神经系统的免疫调节作用

Neuroendocrine-immune regulatory network consists of nervous, endocrine and immune system, and these three systems can be optimized each other through various signal molecules including neurotransmitters, hormones and cytokines to maintain the host homeostasis. Cholinergic nervous system is a vital part in the regulatory network, and play important role in the immune defence. In the present research, the immunomodulation of cholinergic nervous system in scallop will be investigated through the modern biological techniques. The activatory cholinergic neurons are detected in scallop ganglions after pathogen challenge to understand the activation of scallop cholinergic nervous system in the immune response. After acetylcholine or its metabolic enzyme inhibitors treatment, the temporal changes of cellular and humoral immune parameters are examined to cognize the regulatory mode of cholinergic nervous system on scallop innate immune response. The fluctuation of second messenger,active immune transcription factor and the expression of some immune-related genes are measured after the blockage of nicotinic acetylcholine receptors in the haemocytes to explore the signal transduction pathway in the immunomodulation of scallop cholinergic nervous system. The expected results would contribute to further understand the immune defence mechanism of mollusc on the basis of neuroendocrine-immune regulatory network, and be helpful for better knowledge of neuroendocrinology and neuroimmunology in marine invertebrates as well.

神经内分泌免疫调节网络是指由神经系统、内分泌系统和免疫系统构成的，通过神经递质、激素和细胞因子等信号分子进行系统间互惠性优化调节以维持机体内稳态的反馈性作用网络。胆碱能神经系统是神经内分泌免疫调节网络的重要组成部分，在机体免疫防御中发挥着重要作用。本项目拟采用现代生物学技术手段，检测病原感染下扇贝各神经节中活化的胆碱能神经元，确认免疫刺激对扇贝胆碱能神经系统的激活作用；分析乙酰胆碱及其代谢酶抑制剂处理后扇贝细胞和体液免疫指标的变化，明确胆碱能神经系统对扇贝固有免疫应答的调节作用；封闭扇贝血淋巴细胞上的烟碱型乙酰胆碱受体后，检测第二信使水平、入核免疫转录因子含量和免疫相关基因表达的变化，初步确定扇贝胆碱能神经系统调节免疫应答的信号通路。探讨胆碱能神经系统对扇贝免疫应答的调节机制，可以从神经内分泌免疫角度进一步阐释软体动物的免疫防御机制，丰富和发展海洋无脊椎动物的神经内分泌学与神经免疫学内容。

神经内分泌免疫调节网络是指由神经系统、内分泌系统和免疫系统构成的，通过神经递质、激素和细胞因子等信号分子进行系统间互惠性优化调节以维持机体内稳态的反馈性作用网络。胆碱能神经系统是神经内分泌免疫调节网络的重要组成部分，在机体免疫防御中发挥着重要作用。项目执行期间，共获得3 个胆碱能神经系统相关分子的基因，查明了这些基因的表达规律，获得了重组蛋白并验证了其相应的生物学功能，明确了病原相关分子模式刺激和病原菌感染通过免疫细胞因子对扇贝胆碱能神经系统的激活作用，确定了扇贝胆碱能神经系统通过改变代谢酶活性、烟碱型胆碱受体水平和胆碱浓度调控机体细胞和体液免疫应答的方式，并通过二代测序平台解析了贝类扇贝胆碱能神经系统和乙酰胆碱相关miRNA对血淋巴细胞免疫应答的系统调控通路和作用。本项目首次证明了双壳贝类具有原始但完善的胆碱能神经系统，并初步阐明了双壳贝类扇贝胆碱能神经系统的免疫调节作用。胆碱能神经系统对扇贝免疫应答的调节机制研究，从神经内分泌免疫角度进一步阐释了软体动物的免疫防御机制，丰富和发展了海洋无脊椎动物的神经内分泌学与神经免疫学内容。相关研究成果共发表SCI论文3篇。培养研究生2名（其中博士1名，硕士1名）。