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伏马菌素B1通过成熟树突状细胞的细胞骨架重塑和功能衰减发挥免疫抑制作用。

Fumonisin B1 Exerts Immunosuppressive Effects Through Cytoskeleton Remodeling and Function Attenuation of Mature Dendritic Cells.

作者信息

Yu Yanqin, Zhao Xue, Cheng Yao, Shang Guofu, Tang Kaiyi, Wang Yun, Peng Xiaoyan, Ou Sha, Hu Zuquan

机构信息

Immune Cells and Antibody Engineering Research Center in University of Guizhou Province, School of Basic Medical Sciences/School of Biology and Engineering (School of Modern Industry for Health and Medicine), Guizhou Medical University, Guiyang 550025, China.

Guizhou Provincial Engineering Research Center for Smart Biomaterials, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang 550025, China.

出版信息

Int J Mol Sci. 2025 Mar 21;26(7):2876. doi: 10.3390/ijms26072876.

Abstract

Fumonisin B1 (FB1) is one of the most toxic mycotoxins and is harmful to humans and animals due to its hepatotoxicity, immunotoxicity and carcinogenicity. However, the mechanism of its immunosuppressive effect is still under investigation. Dendritic cells (DCs) are the most potent professional antigen-presenting cells, and their differentiation, maturation and immunomodulatory functions are closely related to the immunotoxicity of certain mycotoxins. Migratory capacity is a prerequisite for mature DCs (mDCs) to move and present antigens in secondary lymphoid tissue, whereas the mechanical properties and cytoskeletal structure are critical for their migration and immune functions. Therefore, the effects of FB1 on the cell viability, mechanical characteristics, cytoskeletal structure and its binding proteins, migration, co-stimulatory molecules and the immune functions of mDCs were investigated to explore the potential mechanisms of immunotoxicity. The results showed that FB1 could impair the chemotactic migratory capability, the expression of co-stimulatory molecules and the ability of DCs to stimulate T cell proliferation. Further analyses elucidated that the mechanical properties of mDCs were changed, the cytoskeletal structures were reorganized and the expressions of cytoskeleton-binding proteins were regulated. In conclusion, the attenuated migration and immune functions of mDCs caused by FB1 may be related to their altered mechanical properties and cytoskeleton remodeling, which may be one of the action modes for FB1 to exert its immunosuppressive effect.

摘要

伏马菌素B1(FB1)是毒性最强的霉菌毒素之一,因其具有肝毒性、免疫毒性和致癌性,对人和动物均有害。然而,其免疫抑制作用的机制仍在研究中。树突状细胞(DCs)是最强大的专职抗原呈递细胞,其分化、成熟和免疫调节功能与某些霉菌毒素的免疫毒性密切相关。迁移能力是成熟DCs(mDCs)在次级淋巴组织中移动和呈递抗原的先决条件,而机械特性和细胞骨架结构对其迁移和免疫功能至关重要。因此,研究了FB1对mDCs的细胞活力、机械特性、细胞骨架结构及其结合蛋白、迁移、共刺激分子和免疫功能的影响,以探讨免疫毒性的潜在机制。结果表明,FB1可损害趋化迁移能力、共刺激分子的表达以及DCs刺激T细胞增殖的能力。进一步分析表明,mDCs的机械特性发生改变,细胞骨架结构重新组织,细胞骨架结合蛋白的表达受到调节。总之,FB1导致mDCs迁移和免疫功能减弱可能与其机械特性改变和细胞骨架重塑有关,这可能是FB1发挥免疫抑制作用的作用模式之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de08/11988462/39d2b988baf6/ijms-26-02876-g001.jpg

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