Immune Cells and Antibody Engineering Research Center of Guizhou Province/Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, Guizhou, China.
School of Biology and Engineering, Guizhou Medical University, Guiyang, Guizhou, China.
Biol Trace Elem Res. 2021 Sep;199(9):3360-3370. doi: 10.1007/s12011-020-02449-5. Epub 2020 Oct 26.
Selenium levels can regulate the function of T cells, macrophages, B cells, natural killer cells and other immune cells. However, the effect of selenium on the immune function of dendritic cells (DCs) isolated from selenium-supplemented mice is unknown. In this study, C57BL/6J mice were randomly divided into three groups and fed diets containing low (0.08 ppm), medium (0.25 ppm) or high (1 ppm) selenium levels for 8 weeks. Immature (imDCs) and mature (mDCs) dendritic cells were then isolated from the bone marrow. Next, the migration, phagocytic capacity and mixed lymphocyte reaction (MLR) for imDCs and mDCs were detected by transwell and flow cytometry. The levels of C-C chemokine receptor type 7 (CCR7), major histocompatibility complex II (MHCII) and reactive oxygen species (ROS) were assayed by flow cytometry. F-actin and superoxide dismutase (SOD) activity was detected by fluorescence microscopy and SOD assay kit, respectively. In addition, the extracellular signal-regulated kinase (ERK), Akt, Ras homolog gene family member A/Rho-associated protein kinase (RhoA/ROCK) signalling, selenoprotein K (SELENOK) and glutathione peroxidase 1 (GPX1) levels were measured by western blot analysis. The results indicated that selenium deficiency enhanced the migration of imDCs by ROS and SELENOK-mediated ERK, Akt and RhoA/ROCK pathways but impaired the antigen uptake of imDCs. Although a high selenium level inhibited the migration of imDCs, it had no effect on phagocytic capacity. For mDCs, low selenium levels impaired free migration, and high levels inhibited the chemotactic migration involved in F-actin and CCR7, respectively. Low and high selenium levels impaired the MLR by inhibiting MHCII surface localisation, which might be related to ROS- and SELENOK-mediated ERK, Akt and RhoA/ROCK signalling pathways. In summary, selenium may regulate the immune function of mouse DCs through the ROS- and SELENOK-mediated ERK, Akt and RhoA/ROCK signalling.
硒水平可以调节 T 细胞、巨噬细胞、B 细胞、自然杀伤细胞和其他免疫细胞的功能。然而，补充硒对分离自补硒小鼠的树突状细胞 (DC) 的免疫功能的影响尚不清楚。在这项研究中，C57BL/6J 小鼠被随机分为三组，分别用含有低 (0.08ppm)、中 (0.25ppm) 或高 (1ppm) 硒水平的饮食喂养 8 周。然后从骨髓中分离出未成熟 (imDCs) 和成熟 (mDCs) 树突状细胞。接下来，通过 Transwell 和流式细胞术检测 imDCs 和 mDCs 的迁移、吞噬能力和混合淋巴细胞反应 (MLR)。通过流式细胞术检测 C-C 趋化因子受体 7 (CCR7)、主要组织相容性复合体 II (MHCII) 和活性氧 (ROS) 的水平。通过荧光显微镜和 SOD 测定试剂盒分别检测 F-肌动蛋白和超氧化物歧化酶 (SOD) 的活性。此外，通过 Western blot 分析测定细胞外信号调节激酶 (ERK)、Akt、Ras 同源基因家族成员 A/Rho 相关蛋白激酶 (RhoA/ROCK) 信号通路、硒蛋白 K (SELENOK) 和谷胱甘肽过氧化物酶 1 (GPX1) 的水平。结果表明，硒缺乏通过 ROS 和 SELENOK 介导的 ERK、Akt 和 RhoA/ROCK 通路增强 imDCs 的迁移，但损害 imDCs 的抗原摄取。虽然高硒水平抑制 imDCs 的迁移，但对其吞噬能力没有影响。对于 mDCs，低硒水平损害了自由迁移，高硒水平分别抑制了与 F-肌动蛋白和 CCR7 相关的趋化性迁移。低硒和高硒水平通过抑制 MHCII 表面定位抑制了 MLR，这可能与 ROS 和 SELENOK 介导的 ERK、Akt 和 RhoA/ROCK 信号通路有关。总之，硒可能通过 ROS 和 SELENOK 介导的 ERK、Akt 和 RhoA/ROCK 信号通路调节小鼠 DCs 的免疫功能。
