伏马菌素B1对树突状细胞迁移和免疫功能影响及机制的研究

Fumonisin B1 (FB1) is an important mycotoxin in nature and seriously detrimental to human and animal health. It has been confirmed that FB1 has a strong immunosuppressive effect, but its specific target and molecular mechanism are still unclear. We deem that dendritic cells (DCs), play a key role in the initiation and regulation of immune responses, should be the important target cells. Our preliminary results showed that FB1 can abnormally remodel the cytoskeleton of DCs, as well as impair their migration capacity. It is well known that the migration capacity of DCs is closely related to its immune functions, and the biophysical properties of cells can reflect the relationship between structure and function. In this study, DCs derived from human peripheral blood mononuclear cells (PBMCs) will be cultured and treated with FB1. Then, the changes of biophysical properties, cytoskeletal structure and its binding proteins, migration capacity, and immune functions of DCs will be detected from the perspective of interdisciplinary science. Besides, the signaling pathway related to maturation, migration and immune function of DCs will be analyzed by RNA sequencing, molecular biology and in vivo animal experiments. After completion of this study, we will ascertain the correlation between the immunosuppressive effect of FB1 and the migration capacity and immune functions of DCs, which can provide the basis for the study of the mechanism of fumonisin induced immunotoxicity.

伏马菌素B1（Fumonisin B1, FB1）是一种严重危害人畜健康的自然界真菌毒素，具有很强的免疫抑制作用，但是具体的作用靶标和分子机制尚不清楚。我们认为，在免疫应答启动和调控中起着关键作用的树突状细胞（Dendritic cells, DCs）应该是重要的靶细胞。本项目的前期研究发现，FB1可以异常重组DCs的细胞骨架并损伤迁移能力。DCs的迁移能力与其免疫学功能密切相关，而细胞的生物物理学特性可以反映其结构和功能的关系。因此，本项目拟从交叉学科的角度利用FB1处理人外周血来源的DCs，检测DCs的生物物理学特性、细胞骨架结构及其结合蛋白、迁移能力和免疫功能的改变，并通过转录组测序、分子生物学和动物体内实验分析FB1对DCs成熟、迁移及免疫功能相关信号通路的影响。本项目的完成，将明确FB1的免疫抑制作用与DCs的迁移能力和免疫功能之间的关系，为伏马菌素免疫毒性机理的研究提供依据。

伏马菌素B1（Fumonisin B1, FB1）是一种严重危害人畜健康的自然界真菌毒素，具有很强的细胞毒性和免疫抑制作用。树突状细胞（Dendritic cells, DCs）在桥连先天性免疫和适应性免疫过程中发挥着关键作用，而内皮细胞（Endothelial cells, ECs）不仅具有屏障功能，还在血管形成、信息传递和机体免疫等方面起着重要作用。本项目在结合免疫学和分子生物学方法分析贵州地区镰刀菌侵染情况及其产生的伏马菌素等毒素化学型的基础上，从交叉学科的角度研究FB1对DCs和ECs的生物物理学特性、细胞骨架结构、迁移能力、脂质代谢和细胞功能的影响。研究结果显示镰刀菌在贵州地区分布广泛、种群丰富，其产毒化学型包括FBs、NIV、NIV+ZEN和DON+ZEN等。同时，研究发现FB1能够影响DCs和ECs的生物物理学特性、迁移能力和细胞功能，其潜在分子机制涉及氧化还原平衡破坏、细胞骨架重组和脂质代谢紊乱等。因此，本研究从生物力学与力学免疫学角度阐述了伏马菌素的免疫抑制作用与其对细胞迁移能力抑制和功能损伤直接相关，为进一步揭示真菌菌素的产毒及毒性机制提供了支撑。