Mechanisms of Dexamethasone inducing generation of tolerogenic dendritic cells

Abstract

Abstract: Dexamethasone belongs to Glucocorticoids and is one kind of widely used immunosuppressive agents in clinical practice.Recent researches have found that in the early stage of immue responses, Dexamethasone works by affecting dendritic cells in vivo. Dexamethasone can restrain specific immune response priming and reduce inflammatory factor releasing by inhibiting differentiation and maturation of dendritic cells, changing phenotype and some important biological functions of dendritic cells.It has become a new focus in basic and clinical medicine to apply Dexamethasone in treatment of autoimmune diseases, tumor, graft rejection reaction and other diseases through its influence on dendritic cells.

Key words: Dexamethasone, dendritic cell, immune tolerance

CLC Number:

R392

HE Xiao-kui, HU Yong-xiu. Mechanisms of Dexamethasone inducing generation of tolerogenic dendritic cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(1): 113-116.

References

[1] Banchereau J, Steinman RM.Dendritic cells and the control of immunity[J]. Nature, 1998, 392(6673):245-252.
[2] Van Duivenvoorde LM, van Mierlo GJ, Boonman ZF, et al. Dendritic cells:Vehicles for tolerance induction and prevention of autoimmune diseases[J]. Immunobiology,2006, 211(6 8):627-632.
[3] Clark AR.Anti-inflammatory functions of glucocorticoidinduced genes[J]. Mol Cell Endocrinol, 2007, 275(1 2):79-97.
[4] Hackstein H, Thomson AW.Dendritic cells:emerging pharmacological targets of immunosuppressive drugs[J]. Immunology, 2004, 4(1):24-34.
[5] Kitajima T, Ariizumi K, Bergstresser PR, et al. A novel mechanism of glucocorticoid-induced immune suppression: the inhibition of T cell-mediated terminal maturation of a murine dendritic cell line[J]. J Clin Invest, 1996, 98(1):142-147.
[6] Abe M, Thomson AW.Dexamethasone preferentially suppresses plasmacytoid dendritic cell differentiation and enhances their apoptotic death[J]. Clin Immunol, 2006, 118(2/3):300-306.
[7] Moser M, Desmedt T, Sornasse T, et al. Glucocorticoids down-regulate dendritic cell function in vitro and in vivo[J]. Eur J Immunol, 1995, 25(10):2818-2824.
[8] Shodell M, Siegal FP.Corticosteroids depress IFN-alphaproducing plasmacytoid dendritic cells in human blood[J]. J Allergy Clin Immunol, 2001, 108(3):446-448.
[9] Van Kooten C, Woltman AM.Dendritic cells as a target of immunosuppressive drugs[J]. Transplant Rev, 2004, 18(2):70-79.
[10] Rozkova D, Horvath R, Bartunkova J, et al. Glucocorticoids severely impair differentiation and antigen presenting function of dendritic cells despite upregulation of Toll-like receptors[J]. Clin Immunol, 2006, 120(3):260-271.
[11] Pan JP, Ju DW,Wang QQ, et al. Dexamethasone inhibits the antigen presentation of dendritic cells in MHC classⅡpathway[J]. Immunol/Lett, 2001, 76(3):153-161.
[12] Xia CQ, Peng R, Beato F, et al. Dexamethasone induces IL-10 producing monocyte-derived dendritic cells with durable immaturity[J]. Scand J Immunol, 2005, 62(1):45-54.
[13] Piemonti L, Monti P, Allavena P, et al. Glucocorticoids affect human dendritic cell differentiation and maturation[J]. J Immunol, 1999, 162(1):6473-6481.
[14] Matyszak MK, Citterio S, Rescigno M, et al. Differential effects of corticosteroids during different stages of dendritic cell maturation[J]. Eur J Immunol, 2000, 30(4):1233-1242.
[15] Rea D, van Kooten C, van Meijgaarden KE, et al. Glucocorticoids transform CD40-triggering of dendritic cells into alternative activation pathway resulting in antigen-presenting cells that secrete IL-10[J]. Blood, 2000, 95(10):3162-3167.
[16] Mainali ES, Tew JG.Dexamethasone selectively inhibits differentiation of cord blood stem cell derived-dendritic cell (DC) precursors into immature DCs[J]. Cell Immunol,2004, 232(1 2):127-136.
[17] Scheinman RI, Cogswell PC, Lofquist AK, et al. Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids[J]. Science, 1995,270(5234):283-286.
[18] Xing NZ, Maldonado ML, Bachman LA, et al. Distinctive dendritic cell modulation by vitamin D3 and glucocorticoid pathway s[J]. Biochem Biophys Res Commun, 2002, 297(3):645-652.
[19] Xia CQ, Kao KJ.Suppression of interleukin-12 production through endogenously secreted interleukin-10 in activated dendritic cells:involvement of activation of extracellular signal-regulated protein kinase[J]. Scand J Immunol, 2003, 58(1):23-32.
[20] Adorini L, Giarratana N, Penna G.Pharmacological induction of tolerogenic dendritic cells and regulatory T cells[J]. Semin Immunol, 2004, 16(2):127-134.
[21] Dong XY, Bachman LA, Kumar R, et al. Generation of antigen-specific, interleukin-10-producing T-cells using dendritic cell stimulation and steroid hormone conditioning[J]. Transpl Immunol, 2003, 11(3 4):323-333.
[22] Duperrier K, Velten FW, Bohlender J, et al. Immunosuppressive agents mediate reduced allostimulatory properties of myeloid-derived dendritic cells despite induction of divergent molecular phenotypes[J]. Mol Immunol, 2005, 42(12):1531-1540.
[23] Li MQ, Wang YY, Guo RW, et al. Glucocorticoids impair microglia ability to induce T cell proliferation and Th1 polarization[J]. Immunol/Lett, 2007, 109(2):129-137.
[24] Koopman G, Dalgleish AG, Bhogal BS, et al. Changes in dendritic cellsubsets in the lymph nodes of rhesus macaques after application of glucocorticoids[J]. Hum Immunol, 2001, 62(3):208-214.
[25] Brokaw JJ, White GW, Baluk P, et al. Glucocorticoid-induced apoptosis of dendritic cells in the rat tracheal mucosa[J]. Am J Respir Cell Mol Biol, 1998, 19(4):598-603.
[26] Matasic R, Dietz AB, Vuk-Pavlovic S.Dexamethasone inhibits dendritic cell maturation by redirecting differentiation of a subset of cells[J]. J Leukoc Biol, 1999, 66(6):909-914.
[27] Abe M, Thomson AW.Influence of immunosuppressive drugs on dendritic cells[J]. Transpl Immunol, 2003, 11(3/4):357-365.