DOI QR코드

DOI QR Code

Maturation-Resistant Dendritic Cells Ameliorate Experimental Autoimmune Uveoretinitis

  • Oh, Keun-Hee (Laboratory of Immunology, Transplantation Research Institute, Seoul National University College of Medicine) ;
  • Kim, Yon-Su (Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Lee, Dong-Sup (Laboratory of Immunology, Transplantation Research Institute, Seoul National University College of Medicine)
  • Received : 2011.10.17
  • Accepted : 2011.11.11
  • Published : 2011.12.31

Abstract

Background: Endogenous uveitis is a chronic inflammatory eye disease of human, which frequently leads to blindness. Experimental autoimmune uveoretinitis (EAU) is an animal disease model of human endogenous uveitis and can be induced in susceptible animals by immunization with retinal antigens. EAU resembles the key immunological characteristics of human disease in that both are $CD4^+$ T-cell mediated diseases. Dendritic cells (DCs) are specialized antigen-presenting cells that are uniquely capable of activating naive T cells. Regulation of immune responses through modulation of DCs has thus been tried extensively. Recently our group reported that donor strain-derived immature DC pretreatment successfully controlled the adverse immune response during allogeneic transplantation. Methods: EAU was induced by immunization with human interphotoreceptor retinoid-binding protein (IRBP) $peptide_{1-20}$. Dendritic cells were differentiated from bone marrow in the presence of recombinant GM-CSF. Results: In this study, we used paraformaldehyde-fixed bone marrow-derived DCs to maintain them in an immature state. Pretreatment with fixed immature DCs, but not fixed mature DCs, ameliorated the disease progression of EAU by inhibiting uveitogenic $CD4^+$ T cell activation and differentiation. Conclusion: Application of iBMDC prepared according to the protocol of this study would provide an important treatment modality for the autoimmune diseases and transplantation rejection.

Keywords

References

  1. Ahn JK, Chung H, Lee DS, Yu YS, Yu HG: CD8brightCD56+ T cells are cytotoxic effectors in patients with active Behcet's uveitis. J Immunol 175;6133-6142, 2005. https://doi.org/10.4049/jimmunol.175.9.6133
  2. Yu HG, Lee DS, Seo JM, Ahn JK, Yu YS, Lee WJ, Chung H: The number of $CD8^{+}$ T cells and NKT cells increases in the aqueous humor of patients with Behçet's uveitis. Clin Exp Immunol 137;437-443, 2004 https://doi.org/10.1111/j.1365-2249.2004.02536.x
  3. Caspi RR, Chan CC, Wiggert B, Chader GJ: The mouse as a model of experimental autoimmune uveoretinitis (EAU). Curr Eye Res 9(Suppl);169-174, 1990.
  4. Nussenblatt RB, Caspi RR, Mahdi R, Chan CC, Roberge F, Lider O, Weiner HL: Inhibition of S-antigen induced experimental autoimmune uveoretinitis by oral induction of tolerance with S-antigen. J Immunol 144;1689-1695, 1990.
  5. Sun B, Rizzo LV, Sun SH, Chan CC, Wiggert B, Wilder RL, Caspi RR: Genetic susceptibility to experimental autoimmune uveitis involves more than a predisposition to generate a T helper-1-like or a T helper-2-like response. J Immunol 159; 1004-1011, 1997.
  6. Turley SJ: Dendritic cells: inciting and inhibiting autoimmunity. Curr Opin Immunol 14;765-770, 2002. https://doi.org/10.1016/S0952-7915(02)00399-0
  7. O'Connell PJ, Li W, Wang Z, Specht SM, Logar AJ, Thomson AW: Immature and mature CD8alpha+ dendritic cells prolong the survival of vascularized heart allografts. J Immunol 168; 143-154, 2002. https://doi.org/10.4049/jimmunol.168.1.143
  8. Steinman RM, Hawiger D, Nussenzweig MC: Tolerogenic dendritic cells. Annu Rev Immunol 21;685-711, 2003. https://doi.org/10.1146/annurev.immunol.21.120601.141040
  9. Wakkach A, Fournier N, Brun V, Breittmayer JP, Cottrez F, Groux H: Characterization of dendritic cells that induce tolerance and T regulatory 1 cell differentiation in vivo. Immunity 18;605-617, 2003. https://doi.org/10.1016/S1074-7613(03)00113-4
  10. Adorini L: Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting autoimmune diabetes. Ann N Y Acad Sci 987;258-261, 2003. https://doi.org/10.1111/j.1749-6632.2003.tb06057.x
  11. Roelen DL, Schuurhuis DH, van den Boogaardt DE, Koekkoek K, van Miert PP, van Schip JJ, Laban S, Rea D, Melief CJ, Offringa R, Ossendorp F, Claas FH: Prolongation of skin graft survival by modulation of the alloimmune response with alternatively activated dendritic cells. Transplantation 76;1608-1615, 2003. https://doi.org/10.1097/01.TP.0000086340.30817.BA
  12. Raimondi G, Thomson AW: Dendritic cells, tolerance and therapy of organ allograft rejection. Contrib Nephrol 146;105-120, 2005.
  13. Kang HG, Lee JE, Yang SH, Lee SH, Gao W, Strom TB, Oh K, Lee DS, Kim YS: Donor-strain-derived immature dendritic cell pre-treatment induced hyporesponsiveness against allogeneic antigens. Immunology 129;567-577, 2010. https://doi.org/10.1111/j.1365-2567.2009.03158.x
  14. Oh K, Byoun OJ, Ham DI, Kim YS, Lee DS: Invariant NKT cells regulate experimental autoimmune uveitis through inhibition of Th17 differentiation. Eur J Immunol 41;392-402, 2011. https://doi.org/10.1002/eji.201040569
  15. Chan CC, Caspi RR, Ni M, Leake WC, Wiggert B, Chader GJ, Nussenblatt RB: Pathology of experimental autoimmune uveoretinitis in mice. J Autoimmun 3;247-255, 1990. https://doi.org/10.1016/0896-8411(90)90144-H
  16. Sun B, Rizzo LV, Sun SH, Chan CC, Wiggert B, Wilder RL, Caspi RR: Genetic susceptibility to experimental autoimmune uveitis involves more than a predisposition to generate a T helper-1-like or a T helper-2-like response. J Immunol 159; 1004-1011, 1997.
  17. Amadi-Obi A, Yu CR, Liu X, Mahdi RM, Clarke GL, Nussenblatt RB, Gery I, Lee YS, Egwuagu CE: TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nat Med 13;711-718, 2007. https://doi.org/10.1038/nm1585
  18. Tang J, Zhu W, Silver PB, Su SB, Chan CC, Caspi RR: Autoimmune uveitis elicited with antigen-pulsed dendritic cells has a distinct clinical signature and is driven by unique effector mechanisms: initial encounter with autoantigen defines disease phenotype. J Immunol 178;5578-5587, 2007. https://doi.org/10.4049/jimmunol.178.9.5578
  19. Luger D, Silver PB, Tang J, Cua D, Chen Z, Iwakura Y, Bowman EP, Sgambellone NM, Chan CC, Caspi RR: Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med 205;799-810, 2008. https://doi.org/10.1084/jem.20071258
  20. Gregori S, Casorati M, Amuchastegui S, Smiroldo S, Davalli AM, Adorini L: Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol 167;1945-1953, 2001. https://doi.org/10.4049/jimmunol.167.4.1945
  21. Hayamizu K, Huie P, Sibley RK, Strober S: Monocyte-derived dendritic cell precursors facilitate tolerance to heart allografts after total lymphoid irradiation. Transplantation 66;1285-1291, 1998. https://doi.org/10.1097/00007890-199811270-00004

Cited by

  1. Immature Dendritic Cell-Derived Exosomes: a Promise Subcellular Vaccine for Autoimmunity vol.36, pp.1, 2013, https://doi.org/10.1007/s10753-012-9539-1
  2. Soluble CD83 Alleviates Experimental Autoimmune Uveitis by Inhibiting Filamentous Actin-Dependent Calcium Release in Dendritic Cells vol.9, pp.None, 2018, https://doi.org/10.3389/fimmu.2018.01567
  3. The pathogenic role of dendritic cells in non-infectious anterior uveitis vol.173, pp.None, 2018, https://doi.org/10.1016/j.exer.2018.05.008
  4. New Insights Into Immunological Therapy for Retinal Disorders vol.11, pp.None, 2011, https://doi.org/10.3389/fimmu.2020.01431
  5. Activated γδ T Cells Promote Dendritic Cell Maturation and Exacerbate the Development of Experimental Autoimmune Uveitis (EAU) in Mice vol.50, pp.2, 2011, https://doi.org/10.1080/08820139.2020.1716786