Spleen and Liver Dendritic Cells Differ in their Tolerogenic and Cytokine Induction Potential
Abstract
Dendritic cells (DCs) play an important role in induction of cellular immune responses. It seems that DCs that reside in different organs may be distinct in their ability to induce immune responses. This study was done to address the differences between spleen and liver DCs in induction of immune response and/or tolerance.
CD11c+ DCs were separated from the liver and spleen of C57BL/6 mice and pulsed with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55. 6×105 MOG35-55 pulsed spleen or liver DCs were injected in foot pad of different groups of mice. Control groups received unpulsed DCs. After 5 days, the mononuclear cells (MNCs) of the regional lymph nodes were isolated from immunized mice for cytokine assays and lymphocyte transformation test. To study the immunologic or tolerogenic effects of DCs, three weeks after immunization of mice with MOG pulsed liver or spleen DCs, experimental autoimmune encephalomyelitis (EAE) was induced in DC-immunized mice by injection of MOG along with complete Freund’s adjuvant. Our results showed that spleen DCs were more potent in stimulating lymph node T cells as illustrated in lymphocyte transformation test. Moreover IL-10 production was higher in mice immunized with liver DCs compared with those immunized with splenic DCs (p=0.017). However, no significant difference in IFN-γ production was observed between two groups. We also found that liver DCs+MOG immunized mice displayed a significantly delayed disease onset compared with spleen DCs+MOG immunized mice and the control groups. The disease score was also milder in liver DCs immunized mice compared with other groups.
It seems that the higher IL-10 production induced by the liver DCs may be one of the main factors in down regulation of immune responses in this organ. It can be concluded also that the liver DCs may inhibit the progress of EAE by shifting the cytokines profile.
1.Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 1973; 137(5):1142-62.
2. Mellman I. Antigen processing and presentation by dendritic cells: cell biological mechanisms. Adv Exp Med Biol 2005; 560:63-7.
3. Granucci F, Zanoni I, Ricciardi-Castagnoli P. Central role of dendritic cells in the regulation and deregulation of immune responses. Cell Mol Life Sci 2008; 65(11):1683-97.
4. Gad M, Claesson MH, Pedersen AE. Dendritic cells in peripheral tolerance and immunity. APMIS 2003; 111(7-8):766-75.
5. Carreno LJ, Riedel CA, Kalergis AM. Induction of tolerogenic dendritic cells by NF-kappaB blockade and Fcgamma receptor modulation. Methods Mol Biol 2011;677:339-53.
6. Matta BM, Castellaneta A, Thomson AW. Tolerogenic plasmacytoid DC. Eur J Immunol 2010; 40(10):2667-76.
7. Vremec D, Pooley J, Hochrein H, Wu L, Shortman K.CD4 and CD8 expression by dendritic cell subtypes in mouse thymus and spleen. J Immunol 2000; 164(6):2978-86.
8. Dunne PJ, Moran B, Cummins RC, Mills KH.CD11c+CD8alpha+ dendritic cells promote protective immunity to respiratory infection with Bordetella pertussis. J Immunol 2009; 183(1):400-10.
9. Reid SD, Penna G, Adorini L. The control of T cell responses by dendritic cell subsets. Curr Opin Immunol 2000; 12(1):114-21.
10. Coquerelle C, Moser M. DC subsets in positive and negative regulation of immunity. Immunol Rev 2010;234(1):317-34.
11. Vremec D, Shortman K. Dendritic cell subtypes in mouse lymphoid organs: cross-correlation of surface markers, changes with incubation, and differences among thymus,spleen, and lymph nodes. J Immunol 1997; 159(2):565-73.
12. Thomson AW, O'Connell PJ, Steptoe RJ, Lu L.Immunobiology of liver dendritic cells. Immunology and cell biology 2002; 80(1):65-73.
13. Lau AH, Thomson AW. Dendritic cells and immune regulation in the liver. Gut 2003; 52(2):307-14.
14. Starzl TE. The "privileged" liver and hepatic tolerogenicity. Liver Transpl 2001; 7(10):918-20.
15. Iwasaki A, Kelsall BL. Freshly isolated Peyer's patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells. J Exp Med 1999; 190(2):229-39.
16. Khanna A, Morelli AE, Zhong C, Takayama T, Lu L, Thomson AW. Effects of liver-derived dendritic cell progenitors on Th1- and Th2-like cytokine responses in vitro and in vivo. J Immunol 2000; 164(3):1346-54.
17. Sumpter TL, Lunz JG, Demetris AJ, Thomson AW.Molecular regulation of hepatic dendritic cell function and its relation to liver transplant outcome. Transplantation 2009; 88(3 Suppl):S40-4.
18. Pillarisetty VG, Miller G, Shah AB, DeMatteo RP. GM- CSF expands dendritic cells and their progenitors in mouse liver. Hepatology 2003; 37(3):641-52.
19. Lu L, Woo J, Rao AS, Li Y, Watkins SC, Qian S, et al.Propagation of dendritic cell progenitors from normal mouse liver using granulocyte/macrophage colony- stimulating factor and their maturational development in the presence of type-1 collagen. J Exp Med 1994;179(6):1823-34.
20. Zarnani AH, Moazzeni SM, Shokri F, Salehnia M, Dokouhaki P, Shojaeian J, et al. The efficient isolation of murine splenic dendritic cells and their cytochemical features. Histochem Cell Biol 2006; 126(2):275-82.
21. Woo J, Lu L, Rao AS, Li Y, Subbotin V, Starzl TE, et al.Isolation, phenotype, and allostimulatory activity of mouse liver dendritic cells. Transplantation 1994;58(4):484-91.
22. Mosayebi G, Ghazavi A, Salehi H, Payani MA, Khazae MR. Effect of sesame oil on the inhibition of experimental autoimmune encephalomyelitis in C57BL/6 mice. Pakistan journal of biological sciences: Pak J Biol Sci 2007; 10(11):1790-6.
23. Helft J, Ginhoux F, Bogunovic M, Merad M. Origin and functional heterogeneity of non-lymphoid tissue dendritic cells in mice. Immunol rev 2010; 234(1):55-75.
24. Bros M, Jahrling F, Renzing A, Wiechmann N, Dang NA, Sutter A, et al. A newly established murine immature dendritic cell line can be differentiated into a mature state, but exerts tolerogenic function upon maturation in the presence of glucocorticoid. Blood 2007; 109(9):3820-9.
25. Lu L, Thomson AW. Manipulation of dendritic cells for tolerance induction in transplantation and autoimmune disease. Transplantation 2002; 73(1 Suppl):S19-22.
26. Karimi MH, Ebadi P, Pourfathollah AA, Moazzeni SM.Tolerance Induction by CD40 Blocking through Specific Antibody in Dendritic Cells. Iran J Allergy Asthma Immunol 2010; 9(3):141-147.
27. Abediankenari S, Ghasemi M. Generation of Immune Inhibitory Dendritic Cells and CD4+T Regulatory Cells Inducing by TGF-β. Iran J Allergy Asthma Immunol 2009; 8(1): 25-30.
28. Steinman RM. The control of immunity and tolerance by dendritic cell. Pathol boil(Paris) 2003; 51(2):59-60.
29. Li M, Zhang X, Zheng X, Lian D, Zhang ZX, Ge W, et al. Immune modulation and tolerance induction by RelB- silenced dendritic cells through RNA interference. J Immunol 2007; 178(9):5480-7.
30. Xia S, Guo Z, Xu X, Yi H, Wang Q, Cao X. Hepatic microenvironment programs hematopoietic progenitor differentiation into regulatory dendritic cells, maintaining liver tolerance. Blood 2008; 112(8):3175-85.
31. Tiegs G, Lohse AW. Immune tolerance: what is unique about the liver. J Autoimmun 2010; 34(1):1-6. 32. Du S, Sandoval F, Trinh P, Umeda E, Voskuhl R.Estrogen receptor-beta ligand treatment modulates dendritic cells in the target organ during autoimmune demyelinating disease. Eur J Immunol 2011; 41(1):140-50
33. Aghdami N, Gharibdoost F, Moazzeni SM. Experimental autoimmune encephalomyelitis (EAE) induced by antigen pulsed dendritic cells in the C57BL/6 mouse: influence of injection route. Experimental animals / Japanese Association for Laboratory Exp Anim 2008; 57(1):45-55.
34. Weir CR, Nicolson K, Backstrom BT. Experimental autoimmune encephalomyelitis induction in naive mice by dendritic cells presenting a self-peptide. Immunol cell biol 2002; 80(1):14-20.
35. Huang YM, Yang JS, Xu LY, Link H, Xiao BG.Autoantigen-pulsed dendritic cells induce tolerance to experimental allergic encephalomyelitis (EAE) in Lewis rats. Clin Exp Immunol 2000; 122(3):437-44.
36. Ko HJ, Chung JY, Nasa Z, Chan J, Siatskas C, Toh BH, et al. Targeting MOG expression to dendritic cells delays onset of experimental autoimmune disease. Autoimmunity 2010; 44(3):177-87.
37. Salomon B, Cohen JL, Masurier C, Klatzmann D. Three populations of mouse lymph node dendritic cells with different origins and dynamics. J Immunol 1998;160(2):708-17.
38. Maldonado-Lopez R, De Smedt T, Pajak B, Heirman C, Thielemans K, Leo O, et al. Role of CD8alpha+ and CD8alpha- dendritic cells in the induction of primary immune responses in vivo. J Leukoc Biol 1999;66(2):242-6.
39. Wu L, Li CL, Shortman K. Thymic dendritic cell precursors: relationship to the T lymphocyte lineage and phenotype of the dendritic cell progeny. J Exp Med 1996;184(3):903-11.
40. Lian ZX, Okada T, He XS, Kita H, Liu YJ, Ansari AA, et al. Heterogeneity of dendritic cells in the mouse liver: identification and characterization of four distinct populations. J Immunol 2003; 170(5):2323-30. 41. O'Connell PJ, Son YI, Giermasz A, Wang Z, Logar AJ, Thomson AW, et al. Type-1 polarized nature of mouse liver CD8alpha- and CD8alpha+ dendritic cells: tissue- dependent differences offset CD8alpha-related dendritic cell heterogeneity. Eur J Immunol 2003; 33(7):2007-13.
42. Bertolino P. Impaired function of dendritic cells translocating the liver sinusoids: a veto effect contributing to intrahepatic tolerance? Eur J Immunol 2008; 38(4):938-41.
43. Link H, Huang YM, Masterman T, Xiao BG. Vaccination with autologous dendritic cells: from experimental autoimmune encephalomyelitis to multiple sclerosis. J Neuroimmunol 2001; 114(1-2):1-7. 44. Dittel BN, Visintin I, Merchant RM, Janeway CA Jr.Presentation of the self antigen myelin basic protein by dendritic cells leads to experimental autoimmune encephalomyelitis. J Immunol 1999; 163(1):32-9.
45. Ludewig B, Odermatt B, Landmann S, Hengartner H, Zinkernagel RM. Dendritic cells induce autoimmune diabetes and maintain disease via de novo formation of local lymphoid tissue. J Exp Med 1998; 188(8):1493-501.
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Issue | Vol 10, No 3 (2011) | |
Section | Articles | |
Keywords | ||
Cytokines Profile Experimental Autoimmune Encephalomyelitis Liver Dendritic Cells Splenic Dendritic Cells |
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