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Selenium Regulation of the Immune Function of Dendritic Cells in Mice Through the ERK, Akt and RhoA/ROCK Pathways

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Abstract

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.

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Abbreviations

AO:

Average optical

CCR7:

C-C chemokine receptor type 7

DCs:

Dendritic cells

ERK:

Extracellular signal-regulated kinase

GPX1:

Glutathione peroxidase 1

GSH:

Glutathione

IL:

Interleukin

imDCs:

Immature dendritic cells

LPS:

Lipopolysaccharides

MAPK:

Mitogen-activated protein kinases

mDCs:

Mature dendritic cells

MHCII:

Major histocompatibility complex II

MLR:

Mixed lymphocyte reaction

MoDCs:

Monocyte-derived DCs

PBS:

Phosphate-buffered saline

RhoA:

Ras homolog gene family member A

ROCK:

Rho-associated protein kinases

ROS:

Reactive oxygen species

rmGM-CSF:

Recombinant mouse granulocyte-macrophage CSF

rmIL-4:

Recombinant mouse interleukin-4

SELENOK:

Selenoprotein K

SOD:

Superoxide dismutase

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Funding

This research was funded by the National Natural Science Foundation of China (No. 21561006 and No. 21867007), Guizhou Provincial Natural Science Foundation (No. [2019]1258 and No. LH[2016]7372) and Opening fund of Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica (No. BCMM202002).

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Authors and Affiliations

  1. Immune Cells and Antibody Engineering Research Center of Guizhou Province/Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, Guizhou, China

    Liangliang Zhang, Huan Xia, Kaide Xia, Xianmei Liu, Xin Zhang, Jie Dai & Yi Jia

  2. School of Biology and Engineering, Guizhou Medical University, Guiyang, Guizhou, China

    Liangliang Zhang, Huan Xia, Kaide Xia, Xianmei Liu, Xin Zhang, Jie Dai, Zhu Zeng & Yi Jia

  3. School of Basic Medical Science, Guizhou Medical University, Guiyang, Guizhou, China

    Zhu Zeng

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  1. Liangliang Zhang
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Liangliang Zhang and Huan Xia contributed to the work equally and should be regarded as co-first authors

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Zhang, L., Xia, H., Xia, K. et al. Selenium Regulation of the Immune Function of Dendritic Cells in Mice Through the ERK, Akt and RhoA/ROCK Pathways. Biol Trace Elem Res 199, 3360–3370 (2021). https://doi.org/10.1007/s12011-020-02449-5

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