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Selenium can regulate the differentiation and immune function of human dendritic cells

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Abstract

Selenium is an essential trace element that can regulate the function of immnue cells via selenoproteins. However, the effects of selenium on human dendritic cell (DCs) remain unclear. Thus, selenoprotein levels in monocytes, immature DCs (imDCs) and mature DCs (mDCs) treated with or without Na2SeO3 were evaluated using RT-PCR, and then the immune function of imDCs and mDCs was detected by flow cytometry, cell counting and the CCK8 assay. In addition, the effects of Se on cytokine and surface marker expression were investigated by RT-PCR. The results revealed different expression levels of selenoprotein in monocytes, imDCs and mDCs, and selenoproeins could be regulated by Se. Moreover, it was indicated that anti-phagocytic activity was improved by 0.1 µM Se, whereas it was suppressed by 0.2 µM Se in imDCs; The migration of imDCs and mDCs was improved by 0.1 µM Se, whereas their migration was inhibited by treatment with 0.05 or 0.2 µM Se; The mixed lymphocyte reaction of mDCs was improved by 0.1 µM Se, and it was inhibited by 0.05 and 0.2 µM Se. In addition, 0.1 µM Se improved the immune function of DCs through the regulation of CD80, CD86, IL12-p35 and IL12-p40. Wheres 0.05 and 0.2 µM Se impaired immune function of DCs by up-regulation of interleukin (IL-10) in imDCs and down-regulation of CD80, CD86, IL12-p35 and IL12-p40 in mDCs. In conclusion, 0.1 µM Se might improve the immune function of human DCs through selenoproteins.

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References

  • Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 293:245–252

    Article  Google Scholar 

  • Ben SB, Peng B, Wang GC, Li C, Gu HF, Jiang H, Meng XL, Lee BJ, Chen CL (2015) Overexpression of selenoprotein SelK in BGC-823 cells inhibits cell adhesion and migration. Biochemistry 80(10):1344–1353

    CAS  PubMed  Google Scholar 

  • Broome CS, McArdle F, Kyle JA, Andrews F, Lowe NM, Hart CA, Arthur JR, Jackson MJ (2004) An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am J Clin Nutr 80:154–162

    Article  CAS  PubMed  Google Scholar 

  • Cella M, Engering A, Pinet V, Pieiers J, Lanzavecchia A (1997) Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature 388(6644):782–787

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Zhang N, Li T, Guo J, Wang Z, Yang M, Gao L (2012) Human umbilical cord Wharton’s jelly stem cells: Immune property genes assay and effect of transplantation on the immune cells of heart failure patients. Cell Immunol 276(1-2):83–90

    Article  CAS  PubMed  Google Scholar 

  • Curran JE, Jowett JBM, Elliott KS, Gao Y, Gluschenko K, Wang J, Azim DMA, Cai G, Mahaney MC, Comuzzie AG, Dyer TD, Walder KR, Zimmet P, MacCluer JW, Collier GR, Kissebah AH, Blangero J (2005) Genetic variation in selenoprotein S influences inflammatory response. Nat Genet 37(11):1234–1241

    Article  CAS  PubMed  Google Scholar 

  • De Smedt T, Van Mechelen M, De Becker G, Urbain J, Leo O, Moser M (1997) Effect of interleukin-10 on dendritic cell maturation and function. Eur J Immunol 27(5):1229–1235

    Article  PubMed  Google Scholar 

  • Dinh QT, Cui Z, Huang J, Tran TAT, Wang D, Yang W, Zhou F, Wang M, Yu D, Liang D (2018) Selenium distribution in the Chinese environment and its relationship with human health: a review. Environ Int 112:294–309

    Article  CAS  PubMed  Google Scholar 

  • Fahey AJ, Adrian RR, Constantinescu CS (2007) Curcumin modulation of IFN-beta and IL-12 signalling and cytokine induction in human T cells. J Cell Mol Med 11(5):1129–1137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fairweather-Tait SJ, Bao Y, Broadley MR, Collings R, Ford D, Hesketh JE, Hurst R (2011) Selenium in human health and disease. Antioxid Redox Sign 14(7):1337–1383

    Article  CAS  Google Scholar 

  • Förster R, Davalos-Misslitz AC, Rot A (2008) CCR7 and its ligands: balancing immunity and tolerance. Nature Rev Immunol 8(5):362–371

    Article  Google Scholar 

  • Goldson AJ, Fairweather-Tait SJ, Armah CN, Bao Y, Broadley MR, Dainty JR, Furniss C, Hart DJ, Teucher B, Hurst R (2011) Effects of selenium supplementation on selenoprotein gene expression and response to influenza vaccine challenge: a randomised controlled trial. PLoS ONE 6:e14771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hattori H, Imai H, Furuhama K, Sato O, Nakagawa Y (2005) Induction of phospholipid hydroperoxide glutathione peroxidase in human polymorphonuclear neutrophils and HL60 cells stimulated with TNF-alpha. Biochem Biophys Res Commun 337:464–473

    Article  CAS  PubMed  Google Scholar 

  • Hawkes WC, Kelley DS, Taylor PC (2001) The effects of dietary selenium on the immune system in healthy men. Biol Trace Elem Res 81:189–213

    Article  CAS  PubMed  Google Scholar 

  • Hoffmann FKW, Hashimoto AC, Shafer LA, Dow S, Berry MJ, Hoffmann PR (2010) Dietary selenium modulates activation and differentiation of CD4+ T cells in mice through a mechanism involving cellular free thiols. J Nutr 140(6):1155–1161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu Y, Lu J, Xu X, Lyu J, Zhang H (2017) Regulation of focal adhesion turnover in SDF-1α-stimulated migration of mesenchymal stem cells in neural differentiation. Sci Rep 7(1):10013

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang Z, Hoffmann FKW, Norton RL, Hashimoto AC, Hoffmann PR (2011) Selenoprotein K is a novel target of m-calpain, and cleavage is regulated by Toll-like receptor-induced calpastatin in macrophages. J Biol Chemi 286(40):34830–34838

    Article  CAS  Google Scholar 

  • Huang Z, Rose AH, Hoffmann PR (2012) The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Sign 16(7):705–743

    Article  CAS  Google Scholar 

  • Jia Y, Li Y, Du S, Huang K (2012) Involvement of MsrB1 in the regulation of redox balance and inhibition of peroxynitrite-induced apoptosis in human lens epithelial cells. Exp Eye Res 100:7–16

    Article  CAS  PubMed  Google Scholar 

  • Jia Y, Zhou J, Liu H, Huang K (2014) Effect of methionine sulfoxide reductase B1 (SelR) gene silencing on peroxynitrite-induced F-actin disruption in human lens epithelial cells. Biochem Biophys Res Commun 443(3):876–881

    Article  CAS  PubMed  Google Scholar 

  • Khoso PA, Zhang Y, Yin H, Teng X, Li S (2019) Selenium deficiency affects immune function by influencing selenoprotein and cytokine expression in chicken spleen. Biol Trace Elem Res 187(2):506–516

    Article  CAS  PubMed  Google Scholar 

  • Koch F, Stanzl U, Jennewein P, Janke K, Heufler C, Kanpgen E, Romani N, Schuler G (1996) High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J Exp Med 184(2):741–746

    Article  CAS  PubMed  Google Scholar 

  • Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443

    Article  CAS  PubMed  Google Scholar 

  • Labunskyy VM, Yoo MH, Hatfield DL, Gladyshev VN (2009) Sep15, a thioredoxin-like selenoprotein, is involved in the unfolded protein response and differentially regulated by adaptive and acute ER stresses. Biochemistry 48:8458–8465

    Article  CAS  PubMed  Google Scholar 

  • Lanzavecchia A, Sallusto F (2001) Regulation of T cell immunity by dendritic cells. Cell 106(3):263–266

    Article  CAS  PubMed  Google Scholar 

  • Lee BC, Lee SG, Choo MK, Kim JH, Lee HM, Kim S, Fomenko DE, Kim HY, Park JM, Gladyshev VN (2017) Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo. Sci Rep 7(1):5119

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee HJ, Park JS, Yoo HJ, Lee HM, Lee BC, Kim JH (2020) The selenoprotein MsrB1 instructs dendritic cells to induce T-helper 1 immune responses. Antioxidants (Basel) 9(10):1021

    Article  CAS  Google Scholar 

  • Li M, Cheng W, Nie T, Lai H, Hu X, Luo J, Li F, Li H (2018) Selenoprotein K mediates the proliferation, migration, and invasion of human choriocarcinoma cells by negatively regulating human chorionic gonadotropin expression via ERK, p38 MAPK, and Akt signaling pathway. Biol Trace Elem Res 184(1):47–59

    Article  CAS  PubMed  Google Scholar 

  • Liu X, Xia X, Wang X, Zhou J, Sung LA, Long J, Geng X, Zeng Z, Yao W (2021) Tropomodulin1 expression increases upon maturation in dendritic cells and promotes their maturation and immune functions. Front Immunol 11:587441

    Article  PubMed  PubMed Central  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta CT) method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  • Ma X, Yan W, Zheng H, Du Q, Zhang L, Ban Y, Li N, Wei F (2015) Regulation of IL-10 and IL-12 production and function in macrophages and dendritic cells. F1000Research 4:1465

    Article  Google Scholar 

  • Menager MM, Littman DR (2016) Actin dynamics regulates dendritic cell-mediated transfer of HIV-1 to T cells. Cell 164(4):695–709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meng XL, Chen CL, Liu YY, Su SJ, Gou JM, Huan FN, Wang D, Liu HS, Ben SB, Lu J (2019) Selenoprotein SELENOK enhances the migration and phagocytosis of microglial cells by increasing the cytosolic free Ca2+ level resulted from the up-regulation of IP3R. Neuroscience 406:38–49

    Article  CAS  PubMed  Google Scholar 

  • Nelson SM, Lei X, Prabhu KS (2011) Selenium levels affect the IL-4–induced expression of alternative activation markers in murine macrophages. J Nutr 141(9):1754–1761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishimura M, Naito S (2005) Tissue-specific mRNA expression profiles of human toll-like receptors and related genes. Biol Pharm Bull 28(5):886–892

    Article  CAS  PubMed  Google Scholar 

  • Ohno S, Nakajin S (2009) Determination of mRNA expression of human UDP-glucuronosyltransferases and application for localization in various human tissues by real-time reverse transcriptase-polymerase chain reaction. Drug Metab Dispos 37(1):32–40

    Article  CAS  PubMed  Google Scholar 

  • Pan T, Liu T, Tan S, Wan N, Zhang Y, Li S (2018) Lower selenoprotein T expression and immune response in the immune organs of broilers with exudative diathesis due to selenium deficiency. Biol Trace Elem Res 182:364–372

    Article  CAS  PubMed  Google Scholar 

  • Shimosato T, Kitazawa H, Katoh S, Tohno M, Iliev ID, Nagasawa C, Kimura T, Kawai Y, Saito T (2005) Augmentation of T(H)-1 type response by immunoactive AT oligonucleotide from lactic acidbacteria via Toll-like receptor 9 signaling. Biochem Biophys Res Commun 326(4):782–787

    Article  CAS  PubMed  Google Scholar 

  • Squires JE, Stoytchev I, Forry EP, Berry MJ (2007) SBP2 binding affinity is a major determinant in differential selenoprotein mRNA translation and sensitivity to nonsense-mediated decay. Mol Cell Biol 27(22):7848–7855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steinbrink K, Wölfl M, Jonuleit H, Knop J, Enk AH (1997) Induction of tolerance by IL-10-treated dendritic cells. J Immunol 159(10):4772–4780

    Article  CAS  PubMed  Google Scholar 

  • Stoedter M, Renko K, Hog A, Schomburg L (2010) Selenium controls the sex-specific immune response and selenoprotein expression during the acute-phase response in mice. Biochem J 429:43–51

    Article  CAS  PubMed  Google Scholar 

  • Sun Z, Liu C, Pan T, Yao H, Li S (2017) Selenium accelerates chicken dendritic cells differentiation and affects selenoproteins expression. Dev Comp Immunol 77:30–37

    Article  CAS  PubMed  Google Scholar 

  • Sun Z, Xu Z, Wang D, Yao H, Li S (2018) Selenium deficiency inhibits dendritic cells differentiation and immune function, imbalance the Th1/Th2 of dendritic cells. Metallomics 10(5):759–767

    Article  CAS  PubMed  Google Scholar 

  • Tao T, Li S, Zhao A, Zhang Y, Liu W (2012) Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome. Eur J Endocrinol 167(5):705–713

    Article  CAS  PubMed  Google Scholar 

  • Vega L, Rodriguez-Sosa M, Garcia-Montalvo EA, Del Razo LM, Elizondo G (2007) Non-optimal levels of dietary selenomethionine alter splenocyte response and modify oxidative stress markers in female mice. Food Chem Toxicol 45:1147–1153

    Article  CAS  PubMed  Google Scholar 

  • Verma S, Hoffmann FKW, Kumar M, Huang Z, Roe K, Nguyen-Wu E, Hashimoto AS, Hoffmann PR (2011) Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses. J Immunol 186(4):2127–2137

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Li R, Huang Y, Wang M, Yang F, Huang D, Wu C, Li Y, Tang Y, Zhang R, Cheng J (2017) Selenoprotein K modulate intracellular free Ca2+ by regulating expression of calcium homoeostasis endoplasmic reticulum protein. Biochem Biophys Res Commun 484(4):734–739

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Jing J, Yan H, Tang J, Jia G, Liu G, Chen X, Tian G, Cai J, Shang H, Zhao H (2018) Selenium pretreatment alleviated LPS-induced immunological stress via upregulation of several selenoprotein encoding genes in murine RAW264.7 cells. Biol Trace Elem Res 186(2):505–513

    Article  CAS  PubMed  Google Scholar 

  • Wang G, Zhan Q, Wu H (2020) Suppression of lipopolysaccharide-induced activation of RAW 264.7 macrophages by Se-methylseleno-l-cysteine. Int Immunopharmacol 89(Pt A):107040

    Article  CAS  PubMed  Google Scholar 

  • Worbs T, Hammerschmidt SI, Förster R (2017) Dendritic cell migration in health and disease. Nat Rev Immunol 17(1):30–48

    Article  CAS  PubMed  Google Scholar 

  • Wu W, Li D, Feng X, Zhao F, Li C, Zheng S, Lyu J (2021) A pan-cancer study of selenoprotein genes as promising targets for cancer therapy. BMC Med Genom 14(1):78

    Article  Google Scholar 

  • You L, Liu C, Yang ZJ, Li M, Li S (2014) Prediction of selenoprotein T structure and its response to selenium deficiency in chicken immune organs. Biol Trace Elem Res 160:222–231

    Article  CAS  PubMed  Google Scholar 

  • Youssef A, Lihrmann I, Falluel-Morel A, Boukhzar L (2018) Selenoprotein T is a key player in ER proteostasis, endocrine homoeostasis and neuroprotection. Free Radic Biol Med 127:145–152

    Article  Google Scholar 

  • Zeng Z, Liu X, Jiang Y, Wang G, Zhan J, Guo J, Yao W, Sun D, Ka W, Tang Y, Tang J, Wen Z, Chien S (2006) Biophysical studies on the differentiation of human CD14+ monocytes into dendritic cells. Cell Biochem Biophys 45(1):19–30

    Article  PubMed  Google Scholar 

  • Zeng Z, Yao W, Xu X, Xu G, Long J, Wang X, Wen Z, Chien S (2009) Hepatocellular carcinoma cells deteriorate the biophysical properties of dendritic cells. Cell Biochem Biophys 55(1):33–43

    Article  CAS  PubMed  Google Scholar 

  • Zhang M, Tang H, Guo Z, An H, Zhu X, Song W, Guo J, Huang X, Chen T, Wang J, Cao X (2004) Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells. Nat Immunol 5(11):1124–1133

    Article  CAS  PubMed  Google Scholar 

  • Zhang K, Zhao Q, Zhan T, Han Y, Tang C, Zhang J (2020) Effect of different selenium sources on growth performance, tissue selenium content, meat quality, and selenoprotein gene expression in finishing pigs. Biol Trace Elem Res 196(2):463–471

    Article  CAS  PubMed  Google Scholar 

  • Zhang L, Xia H, Xia K, Liu X, Zhang X, Dai J, Zeng Z, Jia Y (2021) Selenium regulation of the immune function of dendritic cells in mice through the ERK, Akt and RhoA/ROCK pathways. Biol Trace Elem Res 199(9):3360–3370

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This research was funded by the National Natural Science Foundation of China (Nos. 21561006 and 21867007), the Science and Technology Foundation of Guizhou Province (Nos. [2019]1258, LH[2016]7372 and LH[2016]7357), and Opening fund of Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica (No. BCMM202002). We give our sincere thanks to Blood Center of Guizhou Province for PBMCs providing and the member of the basic medical science research center of Guizhou Medical University for their help in the analysis.

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  1. Yi Jia and  Liangliang Zhang have contributed to the work equally and should be regarded as co-first authors.

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, 550025, Guizhou, China

    Yi Jia, Liangliang Zhang, Xianmei Liu, Shichao Zhang, Jie Dai, Jiangtao Huang, Jin Chen & Jing Zhou

  2. School of Biology and Engineering, Guizhou Medical University, Guiyang, 550025, Guizhou, China

    Yi Jia, Liangliang Zhang, Xianmei Liu, Shichao Zhang, Jie Dai, Jiangtao Huang, Jin Chen, Yun Wang, Jing Zhou & Zhu Zeng

  3. School of Basic Medical Science, Guizhou Medical University, Guiyang, 550025, Guizhou, China

    Yun Wang & Zhu Zeng

  4. Prenatal Diagnosis Center, Guizhou Provincial People’s Hospital, Guiyang, 550002, Guizhou, China

    Liangliang Zhang

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  1. Yi Jia
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Jia, Y., Zhang, L., Liu, X. et al. Selenium can regulate the differentiation and immune function of human dendritic cells. Biometals 34, 1365–1379 (2021). https://doi.org/10.1007/s10534-021-00347-4

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